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

McCoy, C. J., Paupelin-Vaucelle, H., Gorilak, P., Beneke, T., Varga, V. and Gluenz, E. (2023) ULK4 and Fused/STK36 interact to mediate assembly of a motile flagellum. Molecular Biology of the Cell, (doi: 10.1091/mbc.E22-06-0222) (PMID:36989043) (Early Online Publication)

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Unc-51-like kinase (ULK) family serine-threonine protein kinase homologs 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 indicates a direct interaction between the N-terminus of LmxULK4 and LmxFused. Both proteins display a dispersed localisation 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 localise to mammalian motile cilia and we demonstrate here that ULK4 also localises 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.

Item Type:Articles
Status:Early Online Publication
Glasgow Author(s) Enlighten ID:Gluenz, Dr Eva
Authors: McCoy, C. J., Paupelin-Vaucelle, H., Gorilak, P., Beneke, T., Varga, V., and Gluenz, E.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Molecular Biology of the Cell
Publisher:American Society for Cell Biology
ISSN (Online):1939-4586
Published Online:29 March 2023
Copyright Holders:Copyright © 2023 American Society for Cell Biology
First Published:First published in Molecular Biology of the Cell 2023
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
310607Dissecting the role of the Leishmania flagellum in pathogenicityEva GluenzMedical Research Council (MRC)MR/R000859/2III - Parasitology
311611Host-parasite interactions: the role of the Leishmania flagellum in infectionEva GluenzThe Royal Society (ROYSOC)UF160661III - Parasitology
170547The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/ZIII - Parasitology