ULK4 and Fused/STK36 interact to mediate assembly of a motile flagellum

. 2023 Jun 01 ; 34 (7) : ar66. [epub] 20230329

Jazyk angličtina Země Spojené státy americké Médium print-electronic

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid36989043

Grantová podpora
104627/Z/14/Z Wellcome Trust - United Kingdom
MR/R000859/2 Medical Research Council - United Kingdom
104111/Z/14/Z Wellcome Trust - United Kingdom
MR/R000859/1 Medical Research Council - United Kingdom
Wellcome Trust - United Kingdom
15/16_MSD_836338 Medical Research Council - United Kingdom

Unc-51-like kinase (ULK) family serine-threonine protein kinase homologues have been linked to the function of motile cilia in diverse species. Mutations in Fused/STK36 and ULK4 in mice resulted in hydrocephalus and other phenotypes consistent with ciliary defects. How either protein contributes to the assembly and function of motile cilia is not well understood. Here we studied the phenotypes of ULK4 and Fused gene knockout (KO) mutants in the flagellated protist Leishmania mexicana. Both KO mutants exhibited a variety of structural defects of the flagellum cytoskeleton. Biochemical approaches indicate spatial proximity of these proteins and indicate a direct interaction between the N-terminus of LmxULK4 and LmxFused. Both proteins display a dispersed localization throughout the cell body and flagellum, with enrichment near the flagellar base and tip. The stable expression of LmxULK4 was dependent on the presence of LmxFused. Fused/STK36 was previously shown to localize to mammalian motile cilia, and we demonstrate here that ULK4 also localizes to the motile cilia in mouse ependymal cells. Taken together these data suggest a model where the pseudokinase ULK4 is a positive regulator of the kinase Fused/ STK36 in a pathway required for stable assembly of motile cilia.

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Akiyoshi B, Gull K (2014). Discovery of unconventional kinetochores in kinetoplastids. PubMed PMC

Amos B, Aurrecoechea C, Barba M, Barreto A, Basenko EY, Bazant W, Belnap R, Blevins AS, Bohme U, Brestelli J, et al. (2021). VEuPathDB: the eukaryotic pathogen, vector and host bioinformatics resource center. PubMed PMC

Baker N, Catta-Preta CMC, Neish R, Sadlova J, Powell B, Alves-Ferreira EVC, Geoghegan V, Carnielli JBT, Newling K, Hughes C, et al. (2022). Systematic functional analysis of PubMed PMC

Beneke T, Demay F, Hookway E, Ashman N, Jeffery H, Smith J, Valli J, Becvar T, Myskova J, Lestinova T, et al. (2019). Genetic dissection of a PubMed PMC

Beneke T, Gluenz E (2019). LeishGEdit: A Method for Rapid Gene Knockout and Tagging Using CRISPR-Cas9. PubMed

Beneke T, Madden R, Makin L, Valli J, Sunter J, Gluenz E (2017). A CRISPR Cas9 high-throughput genome editing toolkit for kinetoplastids. PubMed PMC

Chen MH, Gao N, Kawakami T, Chuang PT (2005). Mice deficient in the fused homolog do not exhibit phenotypes indicative of perturbed hedgehog signaling during embryonic development. PubMed PMC

Dean S, Sunter J, Wheeler R \J, Hodkinson I, Gluenz E, Gull K (2015). A toolkit enabling efficient, scalable and reproducible gene tagging in trypanosomatids. PubMed PMC

Delgehyr N, Meunier A, Faucourt M, Bosch Grau M, Strehl L, Janke C, Spassky N (2015). Ependymal cell differentiation, from monociliated to multiciliated cells. PubMed

Edelbusch C, Cindric S, Dougherty GW, Loges NT, Olbrich H, Rivlin J, Wallmeier J, Pennekamp P, Amirav I, Omran H (2017). Mutation of serine/threonine protein kinase 36 (STK36) causes primary ciliary dyskinesia with a central pair defect. PubMed

Fiebig M, Kelly S, Gluenz E (2015). Comparative lifecycle transcriptomics revises PubMed PMC

Gambarotto D, Zwettler FU, Le Guennec M, Schmidt-Cernohorska M, Fortun D, Borgers S, Heine J, Schloetel JG, Reuss M, Unser M, et al. (2019). Imaging cellular ultrastructures using expansion microscopy (U-ExM). PubMed PMC

Geoghegan V, Carnielli JBT, Jones NG, Saldivia M, Antoniou S, Hughes C, Neish R, Dowle A, Mottram JC (2022). CLK1/CLK2-driven signalling at the Leishmania kinetochore is captured by spatially referenced proximity phosphoproteomics. PubMed PMC

Goetz SC, Anderson KV (2010). The primary cilium: a signalling centre during vertebrate development. PubMed PMC

Hoog JL, Gluenz E, Vaughan S, Gull K (2010). Ultrastructural investigation methods for PubMed

Janke C, Montagnac G (2017). Causes and consequences of microtubule acetylation. PubMed

Jones NG, Thomas EB, Brown E, Dickens NJ, Hammarton TC, Mottram JC (2014). Regulators of PubMed PMC

Khalifa AAZ, Ichikawa M, Dai D, Kubo S, Black CS, Peri K, McAlear TS, Veyron S, Yang SK, Vargas J, et al. (2020). The inner junction complex of the cilia is an interaction hub that involves tubulin post-translational modifications. PubMed PMC

Kumar S, Stecher G, Tamura K (2016). MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets. PubMed PMC

Lang B, Zhang L, Jiang G, Hu L, Lan W, Zhao L, Hunter I, Pruski M, Song NN, Huang Y, et al. (2016). Control of cortex development by ULK4, a rare risk gene for mental disorders including schizophrenia. PubMed PMC

Lechtreck KF (2015). IFT-cargo interactions and protein transport in cilia. PubMed PMC

Lee L (2011). Mechanisms of mammalian ciliary motility: insights from primary ciliary dyskinesia genetics. PubMed

Li H, Durbin R (2009). Fast and accurate short read alignment with Burrows-Wheeler transform. PubMed PMC

Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R, 1000 Genome Project Data Processing Subgroup (2009). The Sequence Alignment/Map format and SAMtools. PubMed PMC

Liu M, Guan Z, Shen Q, Lalor P, Fitzgerald U, O’Brien T, Dockery P, Shen S (2016). Ulk4 is essential for ciliogenesis and CSF flow. PubMed PMC

Ma M, Stoyanova M, Rademacher G, Dutcher SK, Brown A, Zhang R (2019). Structure of the decorated ciliary doublet microtubule. PubMed PMC

Maloverjan A, Piirsoo M (2012). Mammalian homologues of Drosophila fused kinase. PubMed

Maloverjan A, Piirsoo M, Kasak L, Peil L, Osterlund T, Kogerman P (2010). Dual function of UNC-51-like kinase 3 (Ulk3) in the Sonic hedgehog signaling pathway. PubMed PMC

Mangeol P, Prevo B, Peterman EJ (2016). KymographClear and KymographDirect: two tools for the automated quantitative analysis of molecular and cellular dynamics using kymographs. PubMed PMC

Merchant M, Evangelista M, Luoh SM, Frantz GD, Chalasani S, Carano RA, van Hoy M, Ramirez J, Ogasawara AK, McFarland LM, et al. (2005). Loss of the serine/threonine kinase fused results in postnatal growth defects and lethality due to progressive hydrocephalus. PubMed PMC

Moreira-Leite FF, Sherwin T, Kohl L, Gull K (2001). A trypanosome structure involved in transmitting cytoplasmic information during cell division. PubMed

Murone M, Luoh SM, Stone D, Li W, Gurney A, Armanini M, Grey C, Rosenthal A, de Sauvage FJ (2000). Gli regulation by the opposing activities of fused and suppressor of fused. PubMed

Nakayama K, Katoh Y (2018). Ciliary protein trafficking mediated by IFT and BBSome complexes with the aid of kinesin-2 and dynein-2 motors. PubMed

Nozawa YI, Yao E, Gacayan R, Xu SM, Chuang PT (2014). Mammalian Fused is essential for sperm head shaping and periaxonemal structure formation during spermatogenesis. PubMed PMC

Nozawa YI, Yao E, Lin C, Yang JH, Wilson CW, Gacayan R, Chuang PT (2013). Fused (Stk36) is a ciliary protein required for central pair assembly and motile cilia orientation in the mammalian oviduct. PubMed

Owa M, Uchihashi T, Yanagisawa HA, Yamano T, Iguchi H, Fukuzawa H, Wakabayashi KI, Ando T, Kikkawa M (2019). Inner lumen proteins stabilize doublet microtubules in cilia and flagella. PubMed PMC

Portran D, Schaedel L, Xu Z, Thery M, Nachury MV (2017). Tubulin acetylation protects long-lived microtubules against mechanical ageing. PubMed PMC

Preat T, Therond P, Lamour-Isnard C, Limbourg-Bouchon B, Tricoire H, Erk I, Mariol MC, Busson D (1990). A putative serine/threonine protein kinase encoded by the segment-polarity fused gene of Drosophila. PubMed

Preuss F, Chatterjee D, Mathea S, Shrestha S, St-Germain J, Saha M, Kannan N, Raught B, Rottapel R, Knapp S (2020). Nucleotide binding, evolutionary insights, and interaction partners of the pseudokinase Unc-51-like kinase 4. PubMed

Ringers C, Olstad EW, Jurisch-Yaksi N (2020). The role of motile cilia in the development and physiology of the nervous system. PubMed PMC

Robinson JT, Thorvaldsdottir H, Winckler W, Guttman M, Lander ES, Getz G, Mesirov JP (2011). Integrative genomics viewer. PubMed PMC

Romano V, de Beer TA, Schwede T (2017). A computational protocol to evaluate the effects of protein mutants in the kinase gatekeeper position on the binding of ATP substrate analogues. PubMed PMC

Roux KJ, Kim DI, Raida M, Burke B (2012). A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells. PubMed PMC

Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, et al. (2012). Fiji: an open-source platform for biological-image analysis. PubMed PMC

Shaner NC, Lambert GG, Chammas A, Ni Y, Cranfill PJ, Baird MA, Sell BR, Allen JR, Day RN, Israelsson M, et al. (2013). A bright monomeric green fluorescent protein derived from Branchiostoma lanceolatum. PubMed PMC

Shaw AS, Kornev AP, Hu J, Ahuja LG, Taylor SS (2014). Kinases and pseudokinases: lessons from RAF. PubMed PMC

Shi Q, Li S, Jia J, Jiang J (2011). The Hedgehog-induced Smoothened conformational switch assembles a signaling complex that activates Fused by promoting its dimerization and phosphorylation. PubMed PMC

Smertenko A, Hewitt SL, Jacques CN, Kacprzyk R, Liu Y, Marcec MJ, Moyo L, Ogden A, Oung HM, Schmidt S, et al. (2018). Phragmoplast microtubule dynamics—a game of zones. PubMed PMC

Stoddard D, Zhao Y, Bayless BA, Gui L, Louka P, Dave D, Suryawanshi S, Tomasi RF, Dupuis-Williams P, Baroud CN, et al. (2018). PubMed PMC

Tang L, Franca-Koh J, Xiong Y, Chen MY, Long Y, Bickford RM, Knecht DA, Iglesias PA, Devreotes PN (2008). tsunami, the PubMed PMC

Tapia Contreras C, Hoyer-Fender S (2020). The WD40-protein CFAP52/WDR16 is a centrosome/basal body protein and localizes to the manchette and the flagellum in male germ cells. PubMed PMC

Ta-Shma A, Perles Z, Yaacov B, Werner M, Frumkin A, Rein AJ, Elpeleg O (2015). A human laterality disorder associated with a homozygous WDR16 deletion. PubMed PMC

Tillberg PW, Chen F, Piatkevich KD, Zhao Y, Yu CC, English BP, Gao L, Martorell A, Suk HJ, Yoshida F, et al. (2016). Protein-retention expansion microscopy of cells and tissues labeled using standard fluorescent proteins and antibodies. PubMed PMC

Trudgian DC, Ridlova G, Fischer R, Mackeen MM, Ternette N, Acuto O, Kessler BM, Thomas B (2011). Comparative evaluation of label-free SINQ normalized spectral index quantitation in the central proteomics facilities pipeline. PubMed

Trudgian DC, Thomas B, McGowan SJ, Kessler BM, Salek M, Acuto O (2010). CPFP: a central proteomics facilities pipeline. PubMed

UniProt Consortium (2021). UniProt: the universal protein knowledgebase in 2021. PubMed PMC

Varga V, Moreira-Leite F, Portman N, Gull K (2017). Protein diversity in discrete structures at the distal tip of the trypanosome flagellum. PubMed PMC

Vogel P, Read RW, Hansen GM, Payne BJ, Small D, Sands AT, Zambrowicz BP (2012). Congenital hydrocephalus in genetically engineered mice. PubMed

Wheeler RJ (2017). Use of chiral cell shape to ensure highly directional swimming in trypanosomes. PubMed PMC

Wheeler RJ, Gluenz E, Gull K (2015). Routes to a 9+0 flagellum: Basal body multipotency and axonemal plasticity. PubMed PMC

Wheeler RJ, Sunter JD, Gull K (2016). Flagellar pocket restructuring through the PubMed PMC

Wilson CW, Nguyen CT, Chen MH, Yang JH, Gacayan R, Huang J, Chen JN, Chuang PT (2009). Fused has evolved divergent roles in vertebrate Hedgehog signalling and motile ciliogenesis. PubMed PMC

Wisniewski JR, Zougman A, Nagaraj N, Mann M (2009). Universal sample preparation method for proteome analysis. PubMed

Woods A, Sherwin T, Sasse R, MacRae TH, Baines AJ, Gull K (1989). Definition of individual components within the cytoskeleton of PubMed

Zhang Y, Mao F, Lu Y, Wu W, Zhang L, Zhao Y (2011). Transduction of the Hedgehog signal through the dimerization of Fused and the nuclear translocation of Cubitus interruptus. PubMed PMC

Zhou Q, An T, Pham KTM, Hu H, Li Z (2018). The CIF1 protein is a master orchestrator of trypanosome cytokinesis that recruits several cytokinesis regulators to the cytokinesis initiation site. PubMed PMC

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