• This record comes from PubMed

Normal Development and Function of T Cells in Proline Rich 7 (Prr7) Deficient Mice

. 2016 ; 11 (9) : e0162863. [epub] 20160922

Status PubMed-not-MEDLINE Language English Country United States Media electronic-ecollection

Document type Journal Article

Grant support
R01 AG039521 NIA NIH HHS - United States

Transmembrane adaptor proteins (TRAPs) are important organisers for the transduction of immunoreceptor-mediated signals. Prr7 is a TRAP that regulates T cell receptor (TCR) signalling and potently induces cell death when overexpressed in human Jurkat T cells. Whether endogenous Prr7 has a similar functional role is currently unknown. To address this issue, we analysed the development and function of the immune system in Prr7 knockout mice. We found that loss of Prr7 partially impairs development of single positive CD4+ T cells in the thymus but has no effect on the development of other T cell subpopulations, B cells, NK cells, or NKT cells. Moreover, Prr7 does not affect the TCR signalling pathway as T cells derived from Prr7 knockout and wild-type animals and stimulated in vitro express the same levels of the activation marker CD69, and retain their ability to proliferate and activate induced cell death programs. Importantly, Prr7 knockout mice retained the capacity to mount a protective immune response when challenged with Listeria monocytogenes infection in vivo. In addition, T cell effector functions (activation, migration, and reactivation) were normal following induction of experimental autoimmune encephalomyelitis (EAE) in Prr7 knockout mice. Collectively, our work shows that loss of Prr7 does not result in a major immune system phenotype and suggests that Prr7 has a dispensable function for TCR signalling.

See more in PubMed

Horejsi V, Zhang W, Schraven B. Transmembrane adaptor proteins: organizers of immunoreceptor signalling. Nat Rev Immunol. 2004;4(8): 603–616. 10.1038/nri1414 PubMed DOI

Simeoni L, Lindquist JA, Smida M, Witte V, Arndt B, Schraven B. Control of lymphocyte development and activation by negative regulatory transmembrane adapter proteins. Immunol Rev. 2008;224: 215–228. 10.1111/j.1600-065X.2008.00656.x PubMed DOI

Stepanek O, Draber P, Horejsi V. Palmitoylated transmembrane adaptor proteins in leukocyte signaling. Cell Signal. 2014;26(5): 895–902. 10.1016/j.cellsig.2014.01.007 PubMed DOI

Fuller DM, Zhang W. Regulation of lymphocyte development and activation by the LAT family of adapter proteins. Immunol Rev. 2009;232(1): 72–83. 10.1111/j.1600-065X.2009.00828.x PubMed DOI PMC

Balagopalan L, Coussens NP, Sherman E, Samelson LE, Sommers CL. The LAT story: a tale of cooperativity, coordination, and choreography. Cold Spring Harb Perspect Biol. 2010;2(8): a005512 10.1101/cshperspect.a005512 PubMed DOI PMC

Zhang W, Sommers CL, Burshtyn DN, Stebbins CC, DeJarnette JB, Trible RP, et al. Essential role of LAT in T cell development. Immunity. 1999;10(3): 323–332. PubMed

Hrdinka M, Draber P, Stepanek O, Ormsby T, Otahal P, Angelisova P, et al. PRR7 is a transmembrane adaptor protein expressed in activated T cells involved in regulation of T cell receptor signaling and apoptosis. J Biol Chem. 2011;286(22): 19617–19629. 10.1074/jbc.M110.175117 PubMed DOI PMC

Murata Y, Doi T, Taniguchi H, Fujiyoshi Y. Proteomic analysis revealed a novel synaptic proline-rich membrane protein (PRR7) associated with PSD-95 and NMDA receptor. Biochem Biophys Res Commun. 2005;327(1): 183–191. 10.1016/j.bbrc.2004.11.154 PubMed DOI

Zhang N, Hartig H, Dzhagalov I, Draper D, He YW. The role of apoptosis in the development and function of T lymphocytes. Cell Res. 2005;15(10): 749–769. 10.1038/sj.cr.7290345 PubMed DOI

Carpenter AC, Bosselut R. Decision checkpoints in the thymus. Nat Immunol. 2010;11(8): 666–673. 10.1038/ni.1887 PubMed DOI PMC

Riera-Sans L, Behrens A. Regulation of alphabeta/gammadelta T cell development by the activator protein 1 transcription factor c-Jun. J Immunol. 2007;178(9): 5690–5700. PubMed

Krammer PH, Arnold R, Lavrik IN. Life and death in peripheral T cells. Nat Rev Immunol. 2007;7(7): 532–542. 10.1038/nri2115 PubMed DOI

Brenner D, Krammer PH, Arnold R. Concepts of activated T cell death. Crit Rev Oncol Hematol. 2008;66(1): 52–64. 10.1016/j.critrevonc.2008.01.002 PubMed DOI

Pamer EG. Immune responses to Listeria monocytogenes. Nat Rev Immunol. 2004;4(10): 812–823. 10.1038/nri1461 PubMed DOI

Lara-Tejero M, Pamer EG. T cell responses to Listeria monocytogenes. Curr Opin Microbiol. 2004;7(1): 45–50. 10.1016/j.mib.2003.12.002 PubMed DOI

Busch DH, Pilip IM, Vijh S, Pamer EG. Coordinate Regulation of Complex T Cell Populations Responding to Bacterial Infection. Immunity. 1998;8(3): 353–362. 10.1016/S1074-7613(00)80540-3 PubMed DOI

Kamm C, Skoberne M, Geginat G. CD8 T cell immunome analysis of Listeria monocytogenes. FEMS Immunol Med Microbiol. 2003;35(3): 235–242. PubMed

Kipp M, van der Star B, Vogel DY, Puentes F, van der Valk P, Baker D, et al. Experimental in vivo and in vitro models of multiple sclerosis: EAE and beyond. Mult Scler Relat Disord. 2012;1(1): 15–28. 10.1016/j.msard.2011.09.002 PubMed DOI

Rangachari M, Kuchroo VK. Using EAE to better understand principles of immune function and autoimmune pathology. J Autoimmun. 2013;45: 31–39. 10.1016/j.jaut.2013.06.008 PubMed DOI PMC

Procaccini C, De Rosa V, Pucino V, Formisano L, Matarese G. Animal models of Multiple Sclerosis. Eur J Pharmacol. 2015;759:182–91. 10.1016/j.ejphar.2015.03.042 PubMed DOI PMC

Peterson LK, Fujinami RS. Inflammation, demyelination, neurodegeneration and neuroprotection in the pathogenesis of multiple sclerosis. J Neuroimmunol. 2007;184(1–2): 37–44. 10.1016/j.jneuroim.2006.11.015 PubMed DOI PMC

Lassmann H, van Horssen J. The molecular basis of neurodegeneration in multiple sclerosis. FEBS Lett. 2011;585(23): 3715–3723. 10.1016/j.febslet.2011.08.004 PubMed DOI

Fletcher JM, Lalor SJ, Sweeney CM, Tubridy N, Mills KH. T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol. 2010;162(1): 1–11. 10.1111/j.1365-2249.2010.04143.x PubMed DOI PMC

Zepp J, Wu L, Li X. IL-17 receptor signaling and T helper 17-mediated autoimmune demyelinating disease. Trends Immunol. 2011;32(5): 232–239. 10.1016/j.it.2011.02.007 PubMed DOI PMC

Xu S, Huo J, Tan JE, Lam KP. Cbp deficiency alters Csk localization in lipid rafts but does not affect T-cell development. Mol Cell Biol. 2005;25(19): 8486–8495. PubMed PMC

Dobenecker MW, Schmedt C, Okada M, Tarakhovsky A. The ubiquitously expressed Csk adaptor protein Cbp is dispensable for embryogenesis and T-cell development and function. Mol Cell Biol. 2005;25(23): 10533–10542. PubMed PMC

Hrdinka M, Horejsi V. PAG—a multipurpose transmembrane adaptor protein. Oncogene. 2014;33(41): 4881–4892. 10.1038/onc.2013.485 PubMed DOI

Kravchick DO, Karpova A, Hrdinka M, Lopez-Rojas J, Iacobas S, Carbonell AU, Iacobas DA, Kreutz MR, Jordan BA. Synaptonuclear messenger PRR7 inhibits c-Jun ubiquitination and regulates NMDA-mediated excitotoxicity. EMBO J. 2016. July 25 pii: e201593070. PubMed PMC

Gregoire C, Simova S, Wang Y, Sansoni A, Richelme S, Schmidt-Giese A, et al. Deletion of the LIME adaptor protein minimally affects T and B cell development and function. Eur J Immunol. 2007;37(11): 3259–3269. 10.1002/eji.200737563 PubMed DOI

Kolsch U, Arndt B, Reinhold D, Lindquist JA, Juling N, Kliche S, et al. Normal T-cell development and immune functions in TRIM-deficient mice. Mol Cell Biol. 2006;26(9): 3639–3648. PubMed PMC

Simeoni L, Posevitz V, Kolsch U, Meinert I, Bruyns E, Pfeffer K, et al. The transmembrane adapter protein SIT regulates thymic development and peripheral T-cell functions. Mol Cell Biol. 2005;25(17): 7557–7568. PubMed PMC

Liu Y, Zhang W. Identification of a new transmembrane adaptor protein that constitutively binds Grb2 in B cells. J Leukoc Biol. 2008;84(3): 842–851. 10.1189/jlb.0208087 PubMed DOI PMC

Zhu M, Granillo O, Wen R, Yang K, Dai X, Wang D, et al. Negative regulation of lymphocyte activation by the adaptor protein LAX. J Immunol. 2005;174(9): 5612–5619. PubMed

Koelsch U, Schraven B, Simeoni L. SIT and TRIM determine T cell fate in the thymus. J Immunol. 2008;181(9): 5930–5939. 181/9/5930. PubMed

Zhu M, Liu Y, Koonpaew S, Granillo O, Zhang W. Positive and negative regulation of FcepsilonRI-mediated signaling by the adaptor protein LAB/NTAL. J Exp Med. 2004;200(8):991–1000. PubMed PMC

Fleming KK, Bovaird JA, Mosier MC, Emerson MR, LeVine SM, Marquis JG. Statistical analysis of data from studies on experimental autoimmune encephalomyelitis. J Neuroimmunol. 2005;170(1–2): 71–84. 10.1016/j.jneuroim.2005.08.020 PubMed DOI

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...