RAB8A

RAB8A, member RAS oncogene family

Ensembl:
ENSG00000167461
UniProt:
P61006
OMIM:
165040
Synonyms:
MEL, RAB8

Cilia effects upon perturbation of RAB8A

Loss-of-function effect:
Shorter cilia

Ciliogenesis screen results (3 screens)

  • Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-3.24) PMID:26167766
  • Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
  • Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Phenotypes

Mouse phenotype:
increased grip strength, decreased lean body mass

Subcellular localization

basal body, centrosome, cilia

Functional category

  • Ciliary assembly/disassembly
  • Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
  • Actin & cytoskeleton regulation
  • Signaling (Hedgehog, GPCRs, ion channels)
  • Ciliary membrane

Function

Rab8 targets vesicles to the cilium and promotes ciliary membrane elongation. It is activated by Rabin8 (17574030, 22433857). I ctivating Rab8 (GDP- bound state) blocks ciliogenesis and induces BBS phenotypes in zebrafish (17574030). Rab8a, Rab8b and Rab10 work synergistically for ciliogenesis (24213529). Rab8a specifically interacts with cenexin/ODF2, a basal body and microtubule binding protein required for cilium biogenesis (17646400). Regulates the trafficking of rhodopsin in photoreceptors. Interacts with RPGR which regulates its activity and localisation. Involved in polarised trafficking of vesicles from the trans-Golgi network (20631154). Involved in serum-starvation-induced ciliogenesis (32669361)

Model organism evidence

Mus musculus (2 references)

LRRK2 kinase modulates glucose-stimulated insulin secretion via RAB8 phosphorylation and ciliogenesis.

SHCBP1 ablation restored ciliogenesis in unciliated ductal carcinoma by promoting the proximity between the midbody remnant (MBR) and centrosome through enhanced Rab8 GTPase activity and Rab8GTP positioning within the MBR.

PMIDs: 40676250, 39312205

Xenopus (1 reference)

The Rab11-Rabin8-Rab8 ciliogenesis complex regulates the expansion of cilia-derived light-sensing organelles, the rod outer segments, via post-Golgi rhodopsin transport carriers (RTCs).

PMIDs: 39774853

Danio rerio (1 reference)

Rab11-Rab8 cascade dynamics in primary cilia and membrane tubules.

PMIDs: 39520683