Joubert syndrome Arl13b functions at ciliary membranes and stabilizes protein transport in Caenorhabditis elegans


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ÇEVİK KAPLAN S., Hori Y., KAPLAN O. İ. , Kida K., Toivenon T., Foley-Fisher C., ...More

JOURNAL OF CELL BIOLOGY, vol.188, no.6, pp.953-969, 2010 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 188 Issue: 6
  • Publication Date: 2010
  • Doi Number: 10.1083/jcb.200908133
  • Journal Name: JOURNAL OF CELL BIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.953-969
  • Abdullah Gül University Affiliated: Yes

Abstract

The small ciliary G protein Arl13b is required for cilium biogenesis and sonic hedgehog signaling and is mutated in patients with Joubert syndrome (JS). In this study, using Caenorhabditis elegans and mammalian cell culture systems, we investigated the poorly understood ciliary and molecular basis of Arl13b function. First, we show that Arl13b/ARL-13 localization is frequently restricted to a proximal ciliary compartment, where it associates with ciliary membranes via palmitoylation modification motifs. Next, we find that loss-of-function C. elegans arl-13 mutants possess defects in cilium morphology and ultrastructure, as well as defects in ciliary protein localization and transport; ciliary transmembrane proteins abnormally accumulate, PKD-2 ciliary abundance is elevated, and anterograde intraflagellar transport (IFT) is destabilized. Finally, we show that arl-13 interacts genetically with other ciliogenic and ciliary transport-associated genes in maintaining cilium structure/morphology and anterograde IFT stability. Together, these data implicate a role for JS-associated Arl13b at ciliary membranes, where it regulates ciliary transmembrane protein localizations and anterograde IFT assembly stability.