Premium
Rab35 controls cilium length, function and membrane composition
Author(s) -
Kuhns Stefanie,
Seixas Cecília,
Pestana Sara,
Tavares Bárbara,
Nogueira Renata,
Jacinto Raquel,
Ramalho José S,
Simpson Jeremy C,
Andersen Jens S,
Echard Arnaud,
Lopes Susana S,
Barral Duarte C,
Blacque Oliver E
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201847625
Subject(s) - cilium , microbiology and biotechnology , smoothened , biology , zebrafish , rab , intraflagellar transport , cytokinesis , ciliopathies , hedgehog signaling pathway , signal transduction , gtpase , biochemistry , flagellum , phenotype , cell , cell division , gene
Rab and Arl guanine nucleotide‐binding (G) proteins regulate trafficking pathways essential for the formation, function and composition of primary cilia, which are sensory devices associated with Sonic hedgehog (Shh) signalling and ciliopathies. Here, using mammalian cells and zebrafish, we uncover ciliary functions for Rab35, a multitasking G protein with endocytic recycling, actin remodelling and cytokinesis roles. Rab35 loss via si RNA s, morpholinos or knockout reduces cilium length in mammalian cells and the zebrafish left‐right organiser (Kupffer's vesicle) and causes motile cilia‐associated left‐right asymmetry defects. Consistent with these observations, GFP ‐Rab35 localises to cilia, as do GEF ( DENND 1B) and GAP ( TBC 1D10A) Rab35 regulators, which also regulate ciliary length and Rab35 ciliary localisation. Mammalian Rab35 also controls the ciliary membrane levels of Shh signalling regulators, promoting ciliary targeting of Smoothened, limiting ciliary accumulation of Arl13b and the inositol polyphosphate 5‐phosphatase ( INPP 5E). Rab35 additionally regulates ciliary PI (4,5)P 2 levels and interacts with Arl13b. Together, our findings demonstrate roles for Rab35 in regulating cilium length, function and membrane composition and implicate Rab35 in pathways controlling the ciliary levels of Shh signal regulators.