RGD Reference Report - NDR2-mediated Rabin8 phosphorylation is crucial for ciliogenesis by switching binding specificity from phosphatidylserine to Sec15. - Rat Genome Database

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NDR2-mediated Rabin8 phosphorylation is crucial for ciliogenesis by switching binding specificity from phosphatidylserine to Sec15.

Authors: Chiba, S  Amagai, Y  Homma, Y  Fukuda, M  Mizuno, K 
Citation: Chiba S, etal., EMBO J. 2013 Mar 20;32(6):874-85. doi: 10.1038/emboj.2013.32. Epub 2013 Feb 22.
RGD ID: 8693350
Pubmed: PMID:23435566   (View Abstract at PubMed)
PMCID: PMC3604723   (View Article at PubMed Central)
DOI: DOI:10.1038/emboj.2013.32   (Journal Full-text)

Primary cilia are antenna-like sensory organelles protruding from the plasma membrane. Defects in ciliogenesis cause diverse genetic disorders. NDR2 was identified as the causal gene for a canine ciliopathy, early retinal degeneration, but its role in ciliogenesis remains unknown. Ciliary membranes are generated by transport and fusion of Golgi-derived vesicles to the pericentrosome, a process requiring Rab11-mediated recruitment of Rabin8, a GDP-GTP exchange factor (GEF) for Rab8, and subsequent Rab8 activation and Rabin8 binding to Sec15, a component of the exocyst that mediates vesicle tethering. This study shows that NDR2 phosphorylates Rabin8 at Ser-272 and defects in this phosphorylation impair preciliary membrane assembly and ciliogenesis, resulting in accumulation of Rabin8-/Rab11-containing vesicles at the pericentrosome. Rabin8 binds to and colocalizes with GTP-bound Rab11 and phosphatidylserine (PS) on pericentrosomal vesicles. The phospho-mimetic S272E mutation of Rabin8 decreases affinity for PS but increases affinity for Sec15. These results suggest that NDR2-mediated Rabin8 phosphorylation is crucial for ciliogenesis by triggering the switch in binding specificity of Rabin8 from PS to Sec15, thereby promoting local activation of Rab8 and ciliary membrane formation.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:P624928693350PMID:23435566IntAct 
protein binding enablesIPIUniProtKB:Q8R3138693350PMID:23435566IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Rab3ip  (RAB3A interacting protein)


Additional Information