Neuronal voltage-gated calcium channels (VGCCs) serve complex yet essential physiological functions via their pivotal role in translating electrical signals into intracellular calcium elevations and associated downstream signalling pathways. There are a number of regulatory mechanisms to ensure a dynamic control of the number of channels embedded in the plasma membrane, whereas alteration of the surface expression of VGCCs has been linked to various disease conditions. Here, we provide an overview of the mechanisms that control the trafficking of VGCCs to and from the plasma membrane, and discuss their implication in pathophysiological conditions and their potential as therapeutic targets.

Department of Physiology and Pharmacology Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute Cumming School of Medicine University of Calgary Calgary Canada

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Prague Czech Republic

Zobrazit více v PubMed

Berridge M.J. (1998) Neuronal calcium signaling. Neuron 21, 13–2610.1016/S0896-6273(00)80510-3 PubMed DOI

Berridge M.J., Bootman M.D., Roderick H.L. (2003) Calcium signalling: dynamics, homeostasis and remodelling. Nat. Rev. Mol. Cell Biol. 4, 517–52910.1038/nrm1155 PubMed DOI

Catterall W.A. (2011) Voltage-gated calcium channels. Cold Spring Harb. Perspect. Biol. 3, a003947.10.1101/cshperspect.a003947 PubMed DOI PMC

Zamponi G.W., Striessnig J., Koschak A., Dolphin A.C. (2015) The physiology, pathology, and pharmacology of voltage-gated calcium channels and their future therapeutic potential. Pharmacol. Rev. 67, 821–87010.1124/pr.114.009654 PubMed DOI PMC

Ertel E.A., Campbell K.P., Harpold M.M., Hofmann F., Mori Y., Perez-Reyes E.. et al. (2000) Nomenclature of voltage-gated calcium channels. Neuron 25, 533–53510.1016/S0896-6273(00)81057-0 PubMed DOI

Simms B.A., Zamponi G.W. (2014) Neuronal voltage-gated calcium channels: structure, function, and dysfunction. Neuron 82, 24–4510.1016/j.neuron.2014.03.016 PubMed DOI

Takahashi M., Seagar M.J., Jones J.F., Reber B.F., Catterall W.A. (1987) Subunit structure of dihydropyridine-sensitive calcium channels from skeletal muscle. Proc. Natl. Acad. Sci. U.S.A. 84, 5478–548210.1073/pnas.84.15.5478 PubMed DOI PMC

Arikkath J., Campbell K.P. (2003) Auxiliary subunits: essential components of the voltage-gated calcium channel complex. Curr. Opin. Neurobiol. 13, 298–30710.1016/S0959-4388(03)00066-7 PubMed DOI

Leuranguer V., Bourinet E., Lory P., Nargeot J. (1998) Antisense depletion of beta-subunits fails to affect T-type calcium channels properties in a neuroblastoma cell line. Neuropharmacology 37, 701–70810.1016/S0028-3908(98)00060-4 PubMed DOI

Dubel S.J., Altier C., Chaumont S., Lory P., Bourinet E., Nargeot J. (2004) Plasma membrane expression of T-type calcium channel alpha(1) subunits is modulated by high voltage-activated auxiliary subunits. J. Biol. Chem. 279, 29263–2926910.1074/jbc.M313450200 PubMed DOI

Bae J., Suh E.J., Lee C. (2010) Interaction of T-type calcium channel Ca(V)3.3 with the β-subunit. Mol. Cells 30, 185–19110.1007/s10059-010-0106-z PubMed DOI

Lipscombe D., Andrade A., Allen S.E. (2013) Alternative splicing: functional diversity among voltage-gated calcium channels and behavioral consequences. Biochim. Biophys. Acta 1828, 1522–152910.1016/j.bbamem.2012.09.018 PubMed DOI PMC

Weiss N., Zamponi G.W. (2012) Regulation of voltage-gated calcium channels by synaptic proteins. Adv. Exp. Med. Biol. 740, 759–77510.1007/978-94-007-2888-2 PubMed DOI

Zamponi G.W. (2015) Calcium channel signaling complexes with receptors and channels. Curr. Mol. Pharmacol. 8, 8–1110.2174/1874467208666150507093116 PubMed DOI

Proft J., Weiss N. (2015) G protein regulation of neuronal calcium channels: back to the future. Mol. Pharmacol. 87, 890–90610.1124/mol.114.096008 PubMed DOI

Dai S., Hall D.D., Hell J.W. (2009) Supramolecular assemblies and localized regulation of voltage-gated ion channels. Physiol. Rev. 89, 411–45210.1152/physrev.00029.2007 PubMed DOI PMC

Maltez J.M., Nunziato D.A., Kim J., Pitt G.S. (2005) Essential Ca(V)beta modulatory properties are AID-independent. Nat. Struct. Mol. Biol. 12, 372–37710.1038/nsmb909 PubMed DOI

McGee A.W., Nunziato D.A., Maltez J.M., Prehoda K.E., Pitt G.S., Bredt D.S. (2004) Calcium channel function regulated by the SH3-GK module in beta subunits. Neuron 42, 89–9910.1016/S0896-6273(04)00149-7 PubMed DOI

Buraei Z., Yang J. (2010) The β subunit of voltage-gated Ca2+ channels. Physiol. Rev. 90, 1461–150610.1152/physrev.00057.2009 PubMed DOI PMC

Pragnell M., De Waard M., Mori Y., Tanabe T., Snutch T.P., Campbell K.P. (1994) Calcium channel beta-subunit binds to a conserved motif in the I-II cytoplasmic linker of the alpha 1-subunit. Nature 368, 67–7010.1038/368067a0 PubMed DOI

Chen Y.H., Li M.H., Zhang Y., He L.L., Yamada Y., Fitzmaurice A.. et al. (2004) Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca2+ channels. Nature 429, 675–68010.1038/nature02641 PubMed DOI

Opatowsky Y., Chen C.C., Campbell K.P., Hirsch J.A. (2004) Structural analysis of the voltage-dependent calcium channel beta subunit functional core and its complex with the alpha 1 interaction domain. Neuron 42, 387–39910.1016/S0896-6273(04)00250-8 PubMed DOI

Van Petegem F., Clark K.A., Chatelain F.C., Minor D.L. (2004) Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain. Nature 429, 671–67510.1038/nature02588 PubMed DOI PMC

Singer D., Biel M., Lotan I., Flockerzi V., Hofmann F., Dascal N. (1991) The roles of the subunits in the function of the calcium channel. Science 253, 1553–155710.1126/science.1716787 PubMed DOI

Hullin R., Singer-Lahat D., Freichel M., Biel M., Dascal N., Hofmann F.. et al. (1992) Calcium channel beta subunit heterogeneity: functional expression of cloned cDNA from heart, aorta and brain. EMBO J. 11, 885–890 PubMed PMC

Stea A., Dubel S.J., Pragnell M., Leonard J.P., Campbell K.P., Snutch T.P. (1993) A beta-subunit normalizes the electrophysiological properties of a cloned N-type Ca2+ channel alpha 1-subunit. Neuropharmacology 32, 1103–111610.1016/0028-3908(93)90005-N PubMed DOI

Berrow N.S., Campbell V., Fitzgerald E.M., Brickley K., Dolphin A.C. (1995) Antisense depletion of beta-subunits modulates the biophysical and pharmacological properties of neuronal calcium channels. J. Physiol. 482, 481–49110.1113/jphysiol.1995.sp020534 PubMed DOI PMC

Meissner M., Weissgerber P., Londoño J.E., Prenen J., Link S., Ruppenthal S.. et al. (2011) Moderate calcium channel dysfunction in adult mice with inducible cardiomyocyte-specific excision of the cacnb2 gene. J. Biol. Chem. 286, 15875–1588210.1074/jbc.M111.227819 PubMed DOI PMC

Wakamori M., Mikala G., Mori Y. (1999) Auxiliary subunits operate as a molecular switch in determining gating behaviour of the unitary N-type Ca2+ channel current in Xenopus oocytes. J. Physiol. 517, 659–67210.1111/j.1469-7793.1999.0659s.x PubMed DOI PMC

Jones L.P., Wei S.K., Yue D.T. (1998) Mechanism of auxiliary subunit modulation of neuronal alpha1E calcium channels. J. Gen. Physiol. 112, 125–14310.1085/jgp.112.2.125 PubMed DOI PMC

Shistik E., Ivanina T., Puri T., Hosey M., Dascal N. (1995) Ca2+ current enhancement by alpha 2/delta and beta subunits in Xenopus oocytes: contribution of changes in channel gating and alpha 1 protein level. J. Physiol. 489, 55–6210.1113/jphysiol.1995.sp021029 PubMed DOI PMC

Luvisetto S., Fellin T., Spagnolo M., Hivert B., Brust P.F., Harpold M.M.. et al. (2004) Modal gating of human CaV2.1 (P/Q-type) calcium channels: I. The slow and the fast gating modes and their modulation by beta subunits. J. Gen. Physiol. 124, 445–46110.1085/jgp.200409034 PubMed DOI PMC

Colecraft H.M., Alseikhan B., Takahashi S.X., Chaudhuri D., Mittman S., Yegnasubramanian V.. et al. (2002) Novel functional properties of Ca(2+) channel beta subunits revealed by their expression in adult rat heart cells. J. Physiol. 541, 435–45210.1113/jphysiol.2002.018515 PubMed DOI PMC

Bichet D., Cornet V., Geib S., Carlier E., Volsen S., Hoshi T.. et al. (2000) The I-II loop of the Ca2+ channel alpha1 subunit contains an endoplasmic reticulum retention signal antagonized by the beta subunit. Neuron 25, 177–19010.1016/S0896-6273(00)80881-8 PubMed DOI

Cornet V., Bichet D., Sandoz G., Marty I., Brocard J., Bourinet E.. et al. (2002) Multiple determinants in voltage-dependent P/Q calcium channels control their retention in the endoplasmic reticulum. Eur. J. Neurosci. 16, 883–89510.1046/j.1460-9568.2002.02168.x PubMed DOI

Altier C., Garcia-Caballero A., Simms B., You H., Chen L., Walcher J.. et al. (2011) The Cavβ subunit prevents RFP2-mediated ubiquitination and proteasomal degradation of L-type channels. Nat. Neurosci. 14, 173–18010.1038/nn.2712 PubMed DOI

Arias J.M., Murbartián J., Vitko I., Lee J.H., Perez-Reyes E. (2005) Transfer of beta subunit regulation from high to low voltage-gated Ca2+ channels. FEBS Lett. 579, 3907–391210.1016/j.febslet.2005.06.008 PubMed DOI

Fang K., Colecraft H.M. (2011) Mechanism of auxiliary β-subunit-mediated membrane targeting of L-type (Ca(V)1.2) channels. J. Physiol. 589, 4437–445510.1113/jphysiol.2011.214247 PubMed DOI PMC

Dolphin A.C. (2013) The α2δ subunits of voltage-gated calcium channels. Biochim. Biophys. Acta 1828, 1541–154910.1016/j.bbamem.2012.11.019 PubMed DOI

Geisler S., Schöpf C.L., Obermair G.J. (2015) Emerging evidence for specific neuronal functions of auxiliary calcium channel α2δ subunits. Gen. Physiol. Biophys. 34, 105–11810.4149/gpb_2014037 PubMed DOI PMC

Mould J., Yasuda T., Schroeder C.I., Beedle A.M., Doering C.J., Zamponi G.W.. et al. (2004) The alpha2delta auxiliary subunit reduces affinity of omega-conotoxins for recombinant N-type (Cav2.2) calcium channels. J. Biol. Chem. 279, 34705–3471410.1074/jbc.M310848200 PubMed DOI

Davies A., Kadurin I., Alvarez-Laviada A., Douglas L., Nieto-Rostro M., Bauer C.S.. et al. (2010) The alpha2delta subunits of voltage-gated calcium channels form GPI-anchored proteins, a posttranslational modification essential for function. Proc. Natl. Acad. Sci. U.S.A. 107, 1654–165910.1073/pnas.0908735107 PubMed DOI PMC

Marais E., Klugbauer N., Hofmann F. (2001) Calcium channel alpha(2)delta subunits-structure and Gabapentin binding. Mol. Pharmacol. 59, 1243–1248 PubMed

Whittaker C.A., Hynes R.O. (2002) Distribution and evolution of von Willebrand/integrin A domains: widely dispersed domains with roles in cell adhesion and elsewhere. Mol. Biol. Cell 13, 3369–338710.1091/mbc.E02-05-0259 PubMed DOI PMC

Anantharaman V., Aravind L. (2000) Cache–a signaling domain common to animal Ca(2+)-channel subunits and a class of prokaryotic chemotaxis receptors. Trends Biochem. Sci. 25, 535–53710.1016/S0968-0004(00)01672-8 PubMed DOI

Chang F.C., Hosey M.M. (1988) Dihydropyridine and phenylalkylamine receptors associated with cardiac and skeletal muscle calcium channels are structurally different. J. Biol. Chem. 263, 18929–18937 PubMed

Witcher D.R., De Waard M., Sakamoto J., Franzini-Armstrong C., Pragnell M., Kahl S.D.. et al. (1993) Subunit identification and reconstitution of the N-type Ca2+ channel complex purified from brain. Science 261, 486–48910.1126/science.8392754 PubMed DOI

Liu H., De Waard M., Scott V.E., Gurnett C.A., Lennon V.A., Campbell K.P. (1996) Identification of three subunits of the high affinity omega-conotoxin MVIIC-sensitive Ca2+ channel. J. Biol. Chem. 271, 13804–1381010.1074/jbc.271.23.13804 PubMed DOI

Felix R., Gurnett C.A., De Waard M., Campbell K.P. (1997) Dissection of functional domains of the voltage-dependent Ca2+ channel alpha2delta subunit. J. Neurosci. 17, 6884–6891 PubMed PMC

Gao B., Sekido Y., Maximov A., Saad M., Forgacs E., Latif F.. et al. (2000) Functional properties of a new voltage-dependent calcium channel alpha(2)delta auxiliary subunit gene (CACNA2D2). J. Biol. Chem. 275, 12237–1224210.1074/jbc.275.16.12237 PubMed DOI PMC

Yasuda T., Chen L., Barr W., McRory J.E., Lewis R.J., Adams D.J.. et al. (2004) Auxiliary subunit regulation of high-voltage activated calcium channels expressed in mammalian cells. Eur. J. Neurosci. 20, 1–1310.1111/j.1460-9568.2004.03434.x PubMed DOI

Barclay J., Balaguero N., Mione M., Ackerman S.L., Letts V.A., Brodbeck J.. et al. (2001) Ducky mouse phenotype of epilepsy and ataxia is associated with mutations in the Cacna2d2 gene and decreased calcium channel current in cerebellar Purkinje cells. J. Neurosci. 21, 6095–6104 PubMed PMC

Brodbeck J., Davies A., Courtney J.M., Meir A., Balaguero N., Canti C.. et al. (2002) The ducky mutation in Cacna2d2 results in altered Purkinje cell morphology and is associated with the expression of a truncated alpha 2 delta-2 protein with abnormal function. J. Biol. Chem. 277, 7684–769310.1074/jbc.M109404200 PubMed DOI

Cantí C., Nieto-Rostro M., Foucault I., Heblich F., Wratten J., Richards M.W.. et al. (2005) The metal-ion-dependent adhesion site in the Von Willebrand factor-A domain of alpha2delta subunits is key to trafficking voltage-gated Ca2+ channels. Proc. Natl. Acad. Sci. U.S.A. 102, 11230–1123510.1073/pnas.0504183102 PubMed DOI PMC

Davies A., Douglas L., Hendrich J., Wratten J., Tran Van Minh A., Foucault I.. et al. (2006) The calcium channel alpha2delta-2 subunit partitions with CaV2.1 into lipid rafts in cerebellum: implications for localization and function. J. Neurosci. 26, 8748–875710.1523/JNEUROSCI.2764-06.2006 PubMed DOI PMC

Hendrich J., Van Minh A.T., Heblich F., Nieto-Rostro M., Watschinger K., Striessnig J.. et al. (2008) Pharmacological disruption of calcium channel trafficking by the alpha2delta ligand gabapentin. Proc. Natl. Acad. Sci. U.S.A. 105, 3628–363310.1073/pnas.0708930105 PubMed DOI PMC

Qin N., Olcese R., Stefani E., Birnbaumer L. (1998) Modulation of human neuronal alpha 1E-type calcium channel by alpha 2 delta-subunit. Am. J. Physiol. 274, C1324–C1331 PubMed

Kadurin I., Ferron L., Rothwell S.W., Meyer J.O., Douglas L.R., Bauer C.S.. et al. (2016) Proteolytic maturation of α2δ represents a checkpoint for activation and neuronal trafficking of latent calcium channels. Elife 5, e21143.10.7554/eLife.21143 PubMed DOI PMC

Bernstein G.M., Jones O.T. (2007) Kinetics of internalization and degradation of N-type voltage-gated calcium channels: role of the alpha2/delta subunit. Cell Calcium 41, 27–4010.1016/j.ceca.2006.04.010 PubMed DOI

Hoppa M.B., Lana B., Margas W., Dolphin A.C., Ryan T.A. (2012) α2δ expression sets presynaptic calcium channel abundance and release probability. Nature 486, 122–125 PubMed PMC

Wu J., Yan Z., Li Z., Yan C., Lu S., Dong M.. et al. (2015) Structure of the voltage-gated calcium channel Cav1.1 complex. Science 350, aad2395. PubMed

Gurnett C.A., Felix R., Campbell K.P. (1997) Extracellular interaction of the voltage-dependent Ca2+ channel alpha2delta and alpha1 subunits. J. Biol. Chem. 272, 18508–1851210.1074/jbc.272.29.18508 PubMed DOI

Field M.J., Li Z., Schwarz J.B. (2007) Ca2+ channel alpha2-delta ligands for the treatment of neuropathic pain. J. Med. Chem. 50, 2569–257510.1021/jm060650z PubMed DOI

Taylor C.P., Angelotti T., Fauman E. (2007) Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res 73, 137–15010.1016/j.eplepsyres.2006.09.008 PubMed DOI

Moore R.A., Wiffen P.J., Derry S., Toelle T., Rice A.S. (2014) Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst. Rev. 10.1002/14651858.CD012188 PubMed DOI PMC

Gee N.S., Brown J.P., Dissanayake V.U., Offord J., Thurlow R., Woodruff G.N. (1996) The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. J. Biol. Chem. 271, 5768–577610.1074/jbc.271.10.5768 PubMed DOI

Gong H.C., Hang J., Kohler W., Li L., Su T.Z. (2001) Tissue-specific expression and gabapentin-binding properties of calcium channel alpha2delta subunit subtypes. J. Membr. Biol. 184, 35–4310.1007/s00232-001-0072-7 PubMed DOI

Brown J.P., Gee N.S. (1998) Cloning and deletion mutagenesis of the alpha2 delta calcium channel subunit from porcine cerebral cortex. Expression of a soluble form of the protein that retains [3H]gabapentin binding activity. J. Biol. Chem. 273, 25458–2546510.1074/jbc.273.39.25458 PubMed DOI

Wang M., Offord J., Oxender D.L., Su T.Z. (1999) Structural requirement of the calcium-channel subunit alpha2delta for gabapentin binding. Biochem. J. 342, 313–32010.1042/bj3420313 PubMed DOI PMC

Bauer C.S., Nieto-Rostro M., Rahman W., Tran-Van-Minh A., Ferron L., Douglas L.. et al. (2009) The increased trafficking of the calcium channel subunit alpha2delta-1 to presynaptic terminals in neuropathic pain is inhibited by the alpha2delta ligand pregabalin. J. Neurosci. 29, 4076–408810.1523/JNEUROSCI.0356-09.2009 PubMed DOI PMC

Tran-Van-Minh A., Dolphin A.C. (2010) The alpha2delta ligand gabapentin inhibits the Rab11-dependent recycling of the calcium channel subunit alpha2delta-2. J. Neurosci. 30, 12856–1286710.1523/JNEUROSCI.2700-10.2010 PubMed DOI PMC

Field M.J., Cox P.J., Stott E., Melrose H., Offord J., Su T.Z.. et al. (2006) Identification of the alpha2-delta-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proc. Natl. Acad. Sci. U.S.A. 103, 17537–1754210.1073/pnas.0409066103 PubMed DOI PMC

Klugbauer N., Dai S., Specht V., Lacinová L., Marais E., Bohn G.. et al. (2000) A family of gamma-like calcium channel subunits. FEBS Lett. 470, 189–19710.1016/S0014-5793(00)01306-5 PubMed DOI

Rousset M., Cens T., Restituito S., Barrere C., Black J.L., McEnery M.W.. et al. (2001) Functional roles of gamma2, gamma3 and gamma4, three new Ca2+ channel subunits, in P/Q-type Ca2+ channel expressed in Xenopus oocytes. J. Physiol. 532, 583–59310.1111/j.1469-7793.2001.0583e.x PubMed DOI PMC

Green P.J., Warre R., Hayes P.D., McNaughton N.C., Medhurst A.D., Pangalos M.. et al. (2001) Kinetic modification of the alpha(1I) subunit-mediated T-type Ca(2+) channel by a human neuronal Ca(2+) channel gamma subunit. J. Physiol. 533, 467–47810.1111/j.1469-7793.2001.0467a.x PubMed DOI PMC

Kang M.G., Chen C.C., Felix R., Letts V.A., Frankel W.N., Mori Y.. et al. (2001) Biochemical and biophysical evidence for gamma 2 subunit association with neuronal voltage-activated Ca2+ channels. J. Biol. Chem. 276, 32917–3292410.1074/jbc.M100787200 PubMed DOI

Moss F.J., Dolphin A.C., Clare J.J. (2003) Human neuronal stargazin-like proteins, gamma2, gamma3 and gamma4; an investigation of their specific localization in human brain and their influence on CaV2.1 voltage-dependent calcium channels expressed in Xenopus oocytes. BMC Neurosci. 4, 23.10.1186/1471-2202-4-23 PubMed DOI PMC

Black J.L. (2003) The voltage-gated calcium channel gamma subunits: a review of the literature. J. Bioenerg. Biomembr. 35, 649–66010.1023/B:JOBB.0000008029.22650.c5 PubMed DOI

Letts V.A. (2005) Stargazer–a mouse to seize. Epilepsy Curr. 5, 161–16510.1111/j.1535-7511.2005.00051.x PubMed DOI PMC

Letts V.A., Felix R., Biddlecome G.H., Arikkath J., Mahaffey C.L., Valenzuela A.. et al. (1998) The mouse stargazer gene encodes a neuronal Ca2+-channel gamma subunit. Nat. Genet. 19, 340–34710.1038/1228 PubMed DOI

Sharp A.H., Black J.L., Dubel S.J., Sundarraj S., Shen J.P., Yunker A.M.. et al. (2001) Biochemical and anatomical evidence for specialized voltage-dependent calcium channel gamma isoform expression in the epileptic and ataxic mouse, stargazer. Neuroscience 105, 599–61710.1016/S0306-4522(01)00220-2 PubMed DOI

Letts V.A., Kang M.G., Mahaffey C.L., Beyer B., Tenbrink H., Campbell K.P.. et al. (2003) Phenotypic heterogeneity in the stargazin allelic series. Mamm. Genome 14, 506–51310.1007/s00335-003-2268-x PubMed DOI

Zhang Y., Mori M., Burgess D.L., Noebels J.L. (2002) Mutations in high-voltage-activated calcium channel genes stimulate low-voltage-activated currents in mouse thalamic relay neurons. J. Neurosci. 22, 6362–6371 PubMed PMC

Moss F.J., Viard P., Davies A., Bertaso F., Page K.M., Graham A.. et al. (2002) The novel product of a five-exon stargazin-related gene abolishes Ca(V)2.2 calcium channel expression. EMBO J. 21, 1514–152310.1093/emboj/21.7.1514 PubMed DOI PMC

Hansen J.P., Chen R.S., Larsen J.K., Chu P.J., Janes D.M., Weis K.E.. et al. (2004) Calcium channel gamma6 subunits are unique modulators of low voltage-activated (Cav3.1) calcium current. J. Mol. Cell. Cardiol. 37, 1147–115810.1016/j.yjmcc.2004.08.005 PubMed DOI

Lin Z., Witschas K., Garcia T., Chen R.S., Hansen J.P., Sellers Z.M.. et al. (2008) A critical GxxxA motif in the gamma6 calcium channel subunit mediates its inhibitory effect on Cav3.1 calcium current. J. Physiol. 586, 5349–536610.1113/jphysiol.2008.159111 PubMed DOI PMC

Chen R.S., Best P.M. (2009) A small peptide inhibitor of the low voltage-activated calcium channel Cav3.1. Mol. Pharmacol. 75, 1042–105110.1124/mol.108.052654 PubMed DOI

Chen L., Chetkovich D.M., Petralia R.S., Sweeney N.T., Kawasaki Y., Wenthold R.J.. et al. (2000) Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms. Nature 408, 936–94310.1038/35046031 PubMed DOI

Tomita S., Fukata M., Nicoll R.A., Bredt D.S. (2004) Dynamic interaction of stargazin-like TARPs with cycling AMPA receptors at synapses. Science 303, 1508–151110.1126/science.1090262 PubMed DOI

Körber C., Werner M., Kott S., Ma Z.L., Hollmann M. (2007) The transmembrane AMPA receptor regulatory protein gamma 4 is a more effective modulator of AMPA receptor function than stargazin (gamma 2). J. Neurosci. 27, 8442–844710.1523/JNEUROSCI.0424-07.2007 PubMed DOI PMC

Ferron L., Davies A., Page K.M., Cox D.J., Leroy J., Waithe D.. et al. (2008) The stargazin-related protein gamma 7 interacts with the mRNA-binding protein heterogeneous nuclear ribonucleoprotein A2 and regulates the stability of specific mRNAs, including CaV2.2. J. Neurosci. 28, 10604–1061710.1523/JNEUROSCI.2709-08.2008 PubMed DOI PMC

Tselnicker I., Tsemakhovich V.A., Dessauer C.W., Dascal N. (2010) Stargazin modulates neuronal voltage-dependent Ca(2+) channel Ca(v)2.2 by a Gbetagamma-dependent mechanism. J. Biol. Chem. 285, 20462–2047110.1074/jbc.M110.121277 PubMed DOI PMC

Xia Z., Storm D.R. (2005) The role of calmodulin as a signal integrator for synaptic plasticity. Nat. Rev. Neurosci. 6, 267–27610.1038/nrn1647 PubMed DOI

Ben-Johny M., Yue D.T. (2014) Calmodulin regulation (calmodulation) of voltage-gated calcium channels. J. Gen. Physiol. 143, 679–69210.1085/jgp.201311153 PubMed DOI PMC

Ben-Johny M., Dick I.E., Sang L., Limpitikul W.B., Kang P.W., Niu J.. et al. (2015) Towards a unified theory of calmodulin regulation (calmodulation) of voltage-gated calcium and sodium channels. Curr. Mol. Pharmacol. 8, 188–20510.2174/1874467208666150507110359 PubMed DOI PMC

Soong T.W., Mori M.X. (2016) Post-transcriptional modifications and “Calmodulation” of voltage-gated calcium channel function: reflections by two collaborators of David T Yue. Channels (Austin) 10, 14–1910.1080/19336950.2015.1051271 PubMed DOI PMC

Bourdin B., Marger F., Wall-Lacelle S., Schneider T., Klein H., Sauvé R.. et al. (2010) Molecular determinants of the CaVbeta-induced plasma membrane targeting of the CaV1.2 channel. J. Biol. Chem. 285, 22853–2286310.1074/jbc.M110.111062 PubMed DOI PMC

Gao T., Bunemann M., Gerhardstein B.L., Ma H., Hosey M.M. (2000) Role of the C terminus of the alpha 1C (CaV1.2) subunit in membrane targeting of cardiac L-type calcium channels. J. Biol. Chem. 275, 25436–2544410.1074/jbc.M003465200 PubMed DOI

Brunet S., Scheuer T., Klevit R., Catterall W.A. (2005) Modulation of CaV1.2 channels by Mg2+ acting at an EF-hand motif in the COOH-terminal domain. J. Gen. Physiol. 126, 311–32310.1085/jgp.200509333 PubMed DOI PMC

Dolmetsch R.E., Pajvani U., Fife K., Spotts J.M., Greenberg M.E. (2001) Signaling to the nucleus by an L-type calcium channel-calmodulin complex through the MAP kinase pathway. Science 294, 333–33910.1126/science.1063395 PubMed DOI

Peterson B.Z., Lee J.S., Mulle J.G., Wang Y., de Leon M., Yue D.T. (2000) Critical determinants of Ca(2+)-dependent inactivation within an EF-hand motif of L-type Ca(2+) channels. Biophys. J. 78, 1906–192010.1016/S0006-3495(00)76739-7 PubMed DOI PMC

Bernatchez G., Talwar D., Parent L. (1998) Mutations in the EF-hand motif impair the inactivation of barium currents of the cardiac alpha1C channel. Biophys. J. 75, 1727–173910.1016/S0006-3495(98)77614-3 PubMed DOI PMC

Brunet S., Scheuer T., Catterall W.A. (2009) Cooperative regulation of Ca(v)1.2 channels by intracellular Mg(2+), the proximal C-terminal EF-hand, and the distal C-terminal domain. J. Gen. Physiol. 134, 81–9410.1085/jgp.200910209 PubMed DOI PMC

Benmocha A., Almagor L., Oz S., Hirsch J.A., Dascal N. (2009) Characterization of the calmodulin-binding site in the N terminus of CaV1.2. Channels (Austin) 3, 337–34210.4161/chan.3.5.9686 PubMed DOI

Dick I.E., Tadross M.R., Liang H., Tay L.H., Yang W., Yue D.T. (2008) A modular switch for spatial Ca2+ selectivity in the calmodulin regulation of CaV channels. Nature 451, 830–83410.1038/nature06529 PubMed DOI PMC

Simms B.A., Souza I.A., Zamponi G.W. (2014) A novel calmodulin site in the Cav1.2 N-terminus regulates calcium-dependent inactivation. Pflügers Arch. 466, 1793–180310.1007/s00424-013-1423-9 PubMed DOI

Simms B.A., Souza I.A., Rehak R., Zamponi G.W. (2015) The Cav1.2 N terminus contains a CaM kinase site that modulates channel trafficking and function. Pflügers Arch. 467, 677–68610.1007/s00424-014-1538-7 PubMed DOI

Suzuki H., Kawai J., Taga C., Yaoi T., Hara A., Hirose K.. et al. (1996) Stac, a novel neuron-specific protein with cysteine-rich and SH3 domains. Biochem. Biophys. Res. Commun. 229, 902–90910.1006/bbrc.1996.1900 PubMed DOI

Legha W., Gaillard S., Gascon E., Malapert P., Hocine M., Alonso S.. et al. (2010) stac1 and stac2 genes define discrete and distinct subsets of dorsal root ganglia neurons. Gene Expr. Patterns 10, 368–37510.1016/j.gep.2010.08.003 PubMed DOI

Horstick E.J., Linsley J.W., Dowling J.J., Hauser M.A., McDonald K.K., Ashley-Koch A.. et al. (2013) Stac3 is a component of the excitation-contraction coupling machinery and mutated in Native American myopathy. Nat. Commun. 4, 1952.10.1038/ncomms2952 PubMed DOI PMC

Nelson B.R., Wu F., Liu Y., Anderson D.M., McAnally J., Lin W.. et al. (2013) Skeletal muscle-specific T-tubule protein STAC3 mediates voltage-induced Ca2+ release and contractility. Proc. Natl. Acad. Sci. U.S.A. 110, 11881–1188610.1073/pnas.1310571110 PubMed DOI PMC

Bower N.I., de la Serrana D.G., Cole N.J., Hollway G.E., Lee H.T., Assinder S.. et al. (2012) Stac3 is required for myotube formation and myogenic differentiation in vertebrate skeletal muscle. J. Biol. Chem. 287, 43936–4394910.1074/jbc.M112.361311 PubMed DOI PMC

Polster A., Nelson B.R., Olson E.N., Beam K.G. (2016) Stac3 has a direct role in skeletal muscle-type excitation-contraction coupling that is disrupted by a myopathy-causing mutation. Proc. Natl. Acad. Sci. U.S.A. 113, 10986–1099110.1073/pnas.1612441113 PubMed DOI PMC

Polster A., Perni S., Bichraoui H., Beam K.G. (2015) Stac adaptor proteins regulate trafficking and function of muscle and neuronal L-type Ca2+ channels. Proc. Natl. Acad. Sci. U.S.A. 112, 602–60610.1073/pnas.1423113112 PubMed DOI PMC

Weiss N. (2015) Stac gets the skeletal L-type calcium channel unstuck. Gen. Physiol. Biophys. 34, 101–10310.4149/gpb_2015011 PubMed DOI

Vitko I., Bidaud I., Arias J.M., Mezghrani A., Lory P., Perez-Reyes E. (2007) The I-II loop controls plasma membrane expression and gating of Ca(v)3.2 T-type Ca2+ channels: a paradigm for childhood absence epilepsy mutations. J. Neurosci. 27, 322–33010.1523/JNEUROSCI.1817-06.2007 PubMed DOI PMC

Baumgart J.P., Vitko I., Bidaud I., Kondratskyi A., Lory P., Perez-Reyes E. (2008) I-II loop structural determinants in the gating and surface expression of low voltage-activated calcium channels. PLoS One 3, e2976.10.1371/journal.pone.0002976 PubMed DOI PMC

Rzhepetskyy Y., Lazniewska J., Proft J., Campiglio M., Flucher B.E., Weiss N. (2016) A Cav3.2/Stac1 molecular complex controls T-type channel expression at the plasma membrane. Channels (Austin) 10, 346–35410.1080/19336950.2016.1186318 PubMed DOI PMC

Iftinca M.C., Altier C. (2016) Stacking up Cav3.2 channels. Channels (Austin) 11, 1–210.1080/19336950.2016.1242289 PubMed DOI PMC

Aromolaran K.A., Benzow K.A., Cribbs L.L., Koob M.D., Piedras-Rentería E.S. (2009) Kelch-like 1 protein upregulates T-type currents by an actin-F dependent increase in α(1H) channels via the recycling endosome. Channels (Austin) 3, 402–41210.4161/chan.3.6.9858 PubMed DOI

Aromolaran K.A., Benzow K.A., Cribbs L.L., Koob M.D., Piedras-Rentería E.S. (2010) T-type current modulation by the actin-binding protein Kelch-like 1. Am. J. Physiol. Cell Physiol. 298, C1353–C136210.1152/ajpcell.00235.2009 PubMed DOI

Perissinotti P.P., Ethington E.G., Cribbs L., Koob M.D., Martin J., Piedras-Rentería E.S. (2014) Down-regulation of endogenous KLHL1 decreases voltage-gated calcium current density. Cell Calcium 55, 269–28010.1016/j.ceca.2014.03.002 PubMed DOI

Perissinotti P.P., Ethington E.A., Almazan E., Martínez-Hernández E., Kalil J., Koob M.D.. et al. (2014) Calcium current homeostasis and synaptic deficits in hippocampal neurons from Kelch-like 1 knockout mice. Front. Cell Neurosci. 8, 444. PubMed PMC

Felix R., Weiss N. (2016) Ubiquitination and proteasome-mediated degradation of voltage-gated Ca2+ channels and potential pathophysiological implications. Gen. Physiol. Biophys. 36, 1–5 PubMed

Hershko A., Ciechanover A. (1998) The ubiquitin system. Annu. Rev. Biochem. 67, 425–47910.1146/annurev.biochem.67.1.425 PubMed DOI

Rougier J.S., Albesa M., Abriel H., Viard P. (2011) Neuronal precursor cell-expressed developmentally down-regulated 4-1 (NEDD4-1) controls the sorting of newly synthesized Ca(V)1.2 calcium channels. J. Biol. Chem. 286, 8829–883810.1074/jbc.M110.166520 PubMed DOI PMC

Rougier J.S., Albesa M., Syam N., Halet G., Abriel H., Viard P. (2015) Ubiquitin-specific protease USP2-45 acts as a molecular switch to promote α2δ-1-induced downregulation of Cav1.2 channels. Pflügers Arch. 467, 1919–192910.1007/s00424-014-1636-6 PubMed DOI PMC

Waithe D., Ferron L., Page K.M., Chaggar K., Dolphin A.C. (2011) Beta-subunits promote the expression of Ca(V)2.2 channels by reducing their proteasomal degradation. J. Biol. Chem. 286, 9598–961110.1074/jbc.M110.195909 PubMed DOI PMC

Page K.M., Rothwell S.W., Dolphin A.C. (2016) The CaVβ subunit protects the I-II loop of the voltage-gated calcium channel CaV2.2 from proteasomal degradation but not oligoubiquitination. J. Biol. Chem. 291, 20402–2041610.1074/jbc.M116.737270 PubMed DOI PMC

Gandini M.A., Henríquez D.R., Grimaldo L., Sandoval A., Altier C., Zamponi G.W.. et al. (2014) CaV2.2 channel cell surface expression is regulated by the light chain 1 (LC1) of the microtubule-associated protein B (MAP1B) via UBE2L3-mediated ubiquitination and degradation. Pflügers Arch. 466, 2113–212610.1007/s00424-014-1476-4 PubMed DOI

Gandini M.A., Sandoval A., Zamponi G.W., Felix R. (2014) The MAP1B-LC1/UBE2L3 complex catalyzes degradation of cell surface CaV2.2 channels. Channels (Austin) 8, 452–45710.4161/19336950.2014.949162 PubMed DOI PMC

Macabuag N., Dolphin A.C. (2015) Alternative splicing in Ca(V)2.2 regulates neuronal trafficking via adaptor protein complex-1 adaptor protein motifs. J. Neurosci. 35, 14636–1465210.1523/JNEUROSCI.3034-15.2015 PubMed DOI PMC

Marangoudakis S., Andrade A., Helton T.D., Denome S., Castiglioni A.J., Lipscombe D. (2012) Differential ubiquitination and proteasome regulation of Ca(V)2.2 N-type channel splice isoforms. J. Neurosci. 32, 10365–1036910.1523/JNEUROSCI.0851-11.2012 PubMed DOI PMC

García-Caballero A., Gadotti V.M., Stemkowski P., Weiss N., Souza I.A., Hodgkinson V.. et al. (2014) The deubiquitinating enzyme USP5 modulates neuropathic and inflammatory pain by enhancing Cav3.2 channel activity. Neuron 83, 1144–115810.1016/j.neuron.2014.07.036 PubMed DOI

Garcia-Caballero A., Gadotti V.M., Chen L., Zamponi G.W. (2016) A cell-permeant peptide corresponding to the cUBP domain of USP5 reverses inflammatory and neuropathic pain. Mol. Pain 10.1177/1744806916642444 PubMed DOI PMC

Gadotti V.M., Caballero A.G., Berger N.D., Gladding C.M., Chen L., Pfeifer T.A.. et al. (2015) Small organic molecule disruptors of Cav3.2–USP5 interactions reverse inflammatory and neuropathic pain. Mol. Pain 11, 12.10.1186/s12990-015-0011-8 PubMed DOI PMC

Lazniewska J., Weiss N. (2014) The ‘sweet’ side of ion channels. Rev. Physiol. Biochem. Pharmacol. 167, 67–114 PubMed

Park H.J., Min S.H., Won Y.J., Lee J.H. (2015) Asn-linked glycosylation contributes to surface expression and voltage-dependent gating of Cav1.2 Ca2+ channel. J. Microbiol. Biotechnol. 25, 1371–137910.4014/jmb.1501.01066 PubMed DOI

Wang M.C., Collins R.F., Ford R.C., Berrow N.S., Dolphin A.C., Kitmitto A. (2004) The three-dimensional structure of the cardiac L-type voltage-gated calcium channel: comparison with the skeletal muscle form reveals a common architectural motif. J. Biol. Chem. 279, 7159–716810.1074/jbc.M308057200 PubMed DOI

Yunker A.M., Sharp A.H., Sundarraj S., Ranganathan V., Copeland T.D., McEnery M.W. (2003) Immunological characterization of T-type voltage-dependent calcium channel CaV3.1 (alpha 1G) and CaV3.3 (alpha 1I) isoforms reveal differences in their localization, expression, and neural development. Neuroscience 117, 321–33510.1016/S0306-4522(02)00936-3 PubMed DOI

Chen Y., Sharp A.H., Hata K., Yunker A.M., Polo-Parada L., Landmesser L.T.. et al. (2007) Site-directed antibodies to low-voltage-activated calcium channel CaV3.3 (alpha1I) subunit also target neural cell adhesion molecule-180. Neuroscience 145, 981–99610.1016/j.neuroscience.2006.12.060 PubMed DOI

Weiss N., Black S.A., Bladen C., Chen L., Zamponi G.W. (2013) Surface expression and function of Cav3.2 T-type calcium channels are controlled by asparagine-linked glycosylation. Pflügers Arch. 465, 1159–117010.1007/s00424-013-1259-3 PubMed DOI

Orestes P., Osuru H.P., McIntire W.E., Jacus M.O., Salajegheh R., Jagodic M.M.. et al. (2013) Reversal of neuropathic pain in diabetes by targeting glycosylation of Ca(V)3.2 T-type calcium channels. Diabetes 62, 3828–383810.2337/db13-0813 PubMed DOI PMC

Lazniewska J., Rzhepetskyy Y., Zhang F.X., Zamponi G.W., Weiss N. (2016) Cooperative roles of glucose and asparagine-linked glycosylation in T-type calcium channel expression. Pflügers Arch. 468, 1837–185110.1007/s00424-016-1881-y PubMed DOI

Jagodic M.M., Pathirathna S., Nelson M.T., Mancuso S., Joksovic P.M., Rosenberg E.R.. et al. (2007) Cell-specific alterations of T-type calcium current in painful diabetic neuropathy enhance excitability of sensory neurons. J. Neurosci. 27, 3305–331610.1523/JNEUROSCI.4866-06.2007 PubMed DOI PMC

Messinger R.B., Naik A.K., Jagodic M.M., Nelson M.T., Lee W.Y., Choe W.J.. et al. (2009) In vivo silencing of the Ca(V)3.2 T-type calcium channels in sensory neurons alleviates hyperalgesia in rats with streptozocin-induced diabetic neuropathy. Pain 145, 184–19510.1016/j.pain.2009.06.012 PubMed DOI PMC

Latham J.R., Pathirathna S., Jagodic M.M., Choe W.J., Levin M.E., Nelson M.T.. et al. (2009) Selective T-type calcium channel blockade alleviates hyperalgesia in ob/ob mice. Diabetes 58, 2656–266510.2337/db08-1763 PubMed DOI PMC

Duzhyy D.E., Viatchenko-Karpinski V.Y., Khomula E.V., Voitenko N.V., Belan P.V. (2015) Upregulation of T-type Ca2+ channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons. Mol. Pain 11, 29.10.1186/s12990-015-0028-z PubMed DOI PMC

Ondacova K., Karmazinova M., Lazniewska J., Weiss N., Lacinova L. (2016) Modulation of Cav3.2 T-type calcium channel permeability by asparagine-linked glycosylation. Channels (Austin) 10, 175–18410.1080/19336950.2016.1138189 PubMed DOI PMC

Gurnett C.A., De Waard M., Campbell K.P. (1996) Dual function of the voltage-dependent Ca2+ channel alpha 2 delta subunit in current stimulation and subunit interaction. Neuron 16, 431–44010.1016/S0896-6273(00)80061-6 PubMed DOI

Sandoval A., Oviedo N., Andrade A., Felix R. (2004) Glycosylation of asparagines 136 and 184 is necessary for the alpha2delta subunit-mediated regulation of voltage-gated Ca2+ channels. FEBS Lett. 576, 21–2610.1016/j.febslet.2004.08.054 PubMed DOI

Andrade A., Sandoval A., González-Ramírez R., Lipscombe D., Campbell K.P., Felix R. (2009) The alpha(2)delta subunit augments functional expression and modifies the pharmacology of Ca(V)1.3 L-type channels. Cell Calcium 46, 282–29210.1016/j.ceca.2009.08.006 PubMed DOI PMC

Tétreault M.P., Bourdin B., Briot J., Segura E., Lesage S., Fiset C.. et al. (2016) Identification of glycosylation sites essential for surface expression of the CaVα2δ1 subunit and modulation of the cardiac CaV1.2 channel activity. J. Biol. Chem. 291, 4826–484310.1074/jbc.M115.692178 PubMed DOI PMC

Price M.G., Davis C.F., Deng F., Burgess D.L. (2005) The alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate receptor trafficking regulator “stargazin” is related to the claudin family of proteins by Its ability to mediate cell-cell adhesion. J. Biol. Chem. 280, 19711–1972010.1074/jbc.M500623200 PubMed DOI PMC

Sandoval A., Andrade A., Beedle A.M., Campbell K.P., Felix R. (2007) Inhibition of recombinant N-type Ca(V) channels by the gamma 2 subunit involves unfolded protein response (UPR)-dependent and UPR-independent mechanisms. J. Neurosci. 27, 3317–332710.1523/JNEUROSCI.4566-06.2007 PubMed DOI PMC

Obermair G.J., Szabo Z., Bourinet E., Flucher B.E. (2004) Differential targeting of the L-type Ca2+ channel alpha 1C (CaV1.2) to synaptic and extrasynaptic compartments in hippocampal neurons. Eur. J. Neurosci. 19, 2109–212210.1111/j.0953-816X.2004.03272.x PubMed DOI

Tippens A.L., Pare J.F., Langwieser N., Moosmang S., Milner T.A., Smith Y.. et al. (2008) Ultrastructural evidence for pre- and postsynaptic localization of Cav1.2 L-type Ca2+ channels in the rat hippocampus. J. Comp. Neurol. 506, 569–58310.1002/cne.21567 PubMed DOI

Barbado M., Fablet K., Ronjat M., De Waard M. (2009) Gene regulation by voltage-dependent calcium channels. Biochim. Biophys. Acta 1793, 1096–110410.1016/j.bbamcr.2009.02.004 PubMed DOI

Westenbroek R.E., Hell J.W., Warner C., Dubel S.J., Snutch T.P., Catterall W.A. (1992) Biochemical properties and subcellular distribution of an N-type calcium channel alpha 1 subunit. Neuron 9, 1099–111510.1016/0896-6273(92)90069-P PubMed DOI

Westenbroek R.E., Hoskins L., Catterall W.A. (1998) Localization of Ca2+ channel subtypes on rat spinal motor neurons, interneurons, and nerve terminals. J. Neurosci. 18, 6319–6330 PubMed PMC

Westenbroek R.E., Sakurai T., Elliott E.M., Hell J.W., Starr T.V., Snutch T.P.. et al. (1995) Immunochemical identification and subcellular distribution of the alpha 1A subunits of brain calcium channels. J. Neurosci. 15, 6403–6418 PubMed PMC

Hell J.W., Westenbroek R.E., Warner C., Ahlijanian M.K., Prystay W., Gilbert M.M.. et al. (1993) Identification and differential subcellular localization of the neuronal class C and class D L-type calcium channel alpha 1 subunits. J. Cell Biol. 123, 949–96210.1083/jcb.123.4.949 PubMed DOI PMC

Brice N.L., Dolphin A.C. (1999) Differential plasma membrane targeting of voltage-dependent calcium channel subunits expressed in a polarized epithelial cell line. J. Physiol. 515, 685–69410.1111/j.1469-7793.1999.685ab.x PubMed DOI PMC

Wittemann S., Mark M.D., Rettig J., Herlitze S. (2000) Synaptic localization and presynaptic function of calcium channel beta 4-subunits in cultured hippocampal neurons. J. Biol. Chem. 275, 37807–3781410.1074/jbc.M004653200 PubMed DOI

Etemad S., Obermair G.J., Bindreither D., Benedetti A., Stanika R., Di Biase V.. et al. (2014) Differential neuronal targeting of a new and two known calcium channel β4 subunit splice variants correlates with their regulation of gene expression. J. Neurosci. 34, 1446–146110.1523/JNEUROSCI.3935-13.2014 PubMed DOI PMC

Jarvis S.E., Zamponi G.W. (2005) Masters or slaves? Vesicle release machinery and the regulation of presynaptic calcium channels. Cell Calcium 37, 483–48810.1016/j.ceca.2005.01.017 PubMed DOI

Szabo Z., Obermair G.J., Cooper C.B., Zamponi G.W., Flucher B.E. (2006) Role of the synprint site in presynaptic targeting of the calcium channel CaV2.2 in hippocampal neurons. Eur. J. Neurosci. 24, 709–71810.1111/j.1460-9568.2006.04947.x PubMed DOI

Zamponi G.W. (2003) Regulation of presynaptic calcium channels by synaptic proteins. J. Pharmacol. Sci. 92, 79–8310.1254/jphs.92.79 PubMed DOI

Mochida S., Westenbroek R.E., Yokoyama C.T., Zhong H., Myers S.J., Scheuer T.. et al. (2003) Requirement for the synaptic protein interaction site for reconstitution of synaptic transmission by P/Q-type calcium channels. Proc. Natl. Acad. Sci. U.S.A. 100, 2819–282410.1073/pnas.262787699 PubMed DOI PMC

Weiss N., Hameed S., Fernández-Fernández J.M., Fablet K., Karmazinova M., Poillot C.. et al. (2012) A Ca(v)3.2/syntaxin-1A signaling complex controls T-type channel activity and low-threshold exocytosis. J. Biol. Chem. 287, 2810–281810.1074/jbc.M111.290882 PubMed DOI PMC

Jacus M.O., Uebele V.N., Renger J.J., Todorovic S.M. (2012) Presynaptic Cav3.2 channels regulate excitatory neurotransmission in nociceptive dorsal horn neurons. J. Neurosci. 32, 9374–938210.1523/JNEUROSCI.0068-12.2012 PubMed DOI PMC

Weiss N., Zamponi G.W., De Waard M. (2012) How do T-type calcium channels control low-threshold exocytosis. Commun. Integr. Biol. 5, 377–38010.4161/cib.19997 PubMed DOI PMC

Weiss N., Zamponi G.W. (2013) Control of low-threshold exocytosis by T-type calcium channels. Biochim. Biophys. Acta 1828, 1579–158610.1016/j.bbamem.2012.07.031 PubMed DOI

Maximov A., Bezprozvanny I. (2002) Synaptic targeting of N-type calcium channels in hippocampal neurons. J. Neurosci. 22, 6939–6952 PubMed PMC

Hu Q., Saegusa H., Hayashi Y., Tanabe T. (2005) The carboxy-terminal tail region of human Cav2.1 (P/Q-type) channel is not an essential determinant for its subcellular localization in cultured neurones. Genes Cells 10, 87–9610.1111/j.1365-2443.2005.00820.x PubMed DOI

Zhang H., Maximov A., Fu Y., Xu F., Tang T.S., Tkatch T.. et al. (2005) Association of CaV1.3 L-type calcium channels with Shank. J. Neurosci. 25, 1037–104910.1523/JNEUROSCI.4554-04.2005 PubMed DOI PMC

Sheets L., Trapani J.G., Mo W., Obholzer N., Nicolson T. (2011) Ribeye is required for presynaptic Ca(V)1.3a channel localization and afferent innervation of sensory hair cells. Development 138, 1309–131910.1242/dev.059451 PubMed DOI PMC

Morgans C.W. (2001) Localization of the alpha(1F) calcium channel subunit in the rat retina. Invest. Ophthalmol. Vis. Sci. 42, 2414–2418 PubMed

Obermair G.J., Schlick B., Di Biase V., Subramanyam P., Gebhart M., Baumgartner S.. et al. (2010) Reciprocal interactions regulate targeting of calcium channel beta subunits and membrane expression of alpha1 subunits in cultured hippocampal neurons. J. Biol. Chem. 285, 5776–579110.1074/jbc.M109.044271 PubMed DOI PMC

McEnery M.W., Vance C.L., Begg C.M., Lee W.L., Choi Y., Dubel S.J. (1998) Differential expression and association of calcium channel subunits in development and disease. J. Bioenerg. Biomembr. 30, 409–41810.1023/A:1021997924473 PubMed DOI

Tanaka O., Sakagami H., Kondo H. (1995) Localization of mRNAs of voltage-dependent Ca(2+)-channels: four subtypes of alpha 1- and beta-subunits in developing and mature rat brain. Brain Res. Mol. Brain Res. 30, 1–1610.1016/0169-328X(94)00265-G PubMed DOI

Vance C.L., Begg C.M., Lee W.L., Haase H., Copeland T.D., McEnery M.W. (1998) Differential expression and association of calcium channel alpha1B and beta subunits during rat brain ontogeny. J. Biol. Chem. 273, 14495–1450210.1074/jbc.273.23.14495 PubMed DOI

Campiglio M., Di Biase V., Tuluc P., Flucher B.E. (2013) Stable incorporation versus dynamic exchange of β subunits in a native Ca2+ channel complex. J. Cell Sci. 126, 2092–210110.1242/jcs.jcs124537 PubMed DOI PMC

Voigt A., Freund R., Heck J., Missler M., Obermair G.J., Thomas U.. et al. (2016) Dynamic association of calcium channel subunits at the cellular membrane. Neurophotonics 3, 041809.10.1117/1.NPh.3.4.041809 PubMed DOI PMC

Kaur G., Pinggera A., Ortner N.J., Lieb A., Sinnegger-Brauns M.J., Yarov-Yarovoy V.. et al. (2015) A polybasic plasma membrane binding motif in the I-II linker stabilizes voltage-gated CaV1.2 calcium channel function. J. Biol. Chem. 290, 21086–2110010.1074/jbc.M115.645671 PubMed DOI PMC

Scher M.G., Bloch R.J. (1993) Phospholipid asymmetry in acetylcholine receptor clusters. Exp. Cell Res. 208, 485–49110.1006/excr.1993.1270 PubMed DOI

Zamponi G.W. (2016) Targeting voltage-gated calcium channels in neurological and psychiatric diseases. Nat. Rev. Drug Discov. 15, 19–3410.1038/nrd.2015.5 PubMed DOI

Identification of a molecular gating determinant within the carboxy terminal region of Cav3.3 T-type channels