RAB35
RAB35, member RAS oncogene family
- Ensembl:
- ENSG00000111737
- UniProt:
- Q15286
- OMIM:
- 604199
- Synonyms:
- H-RAY
Cilia effects upon perturbation of RAB35
- Cilia number / % ciliated:
- Decreased cilia number
- Loss-of-function effect:
- Shorter cilia
Ciliogenesis screen results (3 screens)
- Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-2.23) PMID:26167766
- Breslow et al. 2018 (CRISPR) [CRISPR]: Negative Regulator (Hh signaling, casTLE effect=0.72) PMID:29459680
- Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381
Phenotypes
- Mouse phenotype:
- preweaning lethality, complete penetrance
- Mouse ciliopathy phenotype:
- cataract, abnormal lens morphology
- Human ciliopathy phenotype:
- Homozygous missense variant (R27H) causes global developmental delay, hydrocephalus, Dandy-Walker malformation, axial hypotonia with peripheral hypertonia, visual problems, conductive hearing impairment.
Ciliopathy associations
- Dandy-Walker Malformation with Neurodevelopmental Delay
Subcellular localization
ciliary membrane
Functional category
- Ciliary assembly/disassembly
- Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
- Actin & cytoskeleton regulation
- Signaling (Hedgehog, GPCRs, ion channels)
- Ciliary membrane
Function
Rab35 at the mammalian and zebrafish cilium regulates cilium length and left‐right asymmetry, and controls the ciliary levels of PI(4,5)P2 and regulators of the Sonic hedgehog pathway. Rab35 GTPase localizes to the ciliary membrane and pocket of mammalian cells and Kupffer's vesicles of zebrafish along with its GAP and GEF.Rab35 depletion leads to formation of shorter cilia in both systems and interferes with left‐ right symmetry formation of zebrafish.Rab35 depletion reduces the levels of Sonic hedgehog signaling components and PI(4,5)P2 in the ciliary membrane. Rab35 interacts with Arl13b and inhibits its ciliary accumulation(PMID: 31432619).
Model organism evidence
Studies in cell lines have indicated that Rab35 participates in cell adhesion, polarity, cytokinesis, and primary cilia length and composition.
Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis.
Rab8, Rab11, and Rab35 coordinate lumen and cilia formation during zebrafish left-right organizer development.
Rab35 loss via siRNAs, 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.