ARHGAP35
Rho GTPase activating protein 35
- Ensembl:
- ENSG00000160007
- UniProt:
- Q9NRY4
- OMIM:
- 605277
- Synonyms:
- GRF-1, GRLF1, KIAA1722, P190A, P190ARHOGAP
Cilia effects upon perturbation of ARHGAP35
- Cilia number / % ciliated:
- Decrease
- Loss-of-function effect:
- Decrease
Ciliogenesis screen results (2 screens)
- Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-3.74) PMID:26167766
- Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
Subcellular localization
basal body, cilia associated gene
Functional category
- Ciliary assembly/disassembly
- Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
- Actin & cytoskeleton regulation
- Neurogenesis & migration
- Signaling (Hedgehog, GPCRs, ion channels)
- Axon guidance & growth
- Cilia length regulation
Function
Using cilia length as a phenotypic readout for centrosomal RhoA activity, ARHGAP5, -29, and -35 as essential regulators of ciliation in normal human re l tubular cells and in PKD1-null cells, centrosomal ARHGAP35 decreased(32663194). ARHGAP35 (p190A RhoGAP) is recruited by FUZ/FUZZY to the basal body where it restricts actin polymerization via RhoA inhibition to allow ciliogenesis. Loss increases actin at basal body → impaired ciliogenesis. Genetic interactions with FUZ confirmed in mice.
Model organism evidence
We discovered that, mechanistically, Fuzzy interacts with and recruits the negative actin regulator ARHGAP35 (also known as p190A RhoGAP) to the basal body.
Using cilia length as a phenotypic readout for centrosomal RhoA activity, we identified ARHGAP5, -29, and -35 as essential regulators of ciliation in normal human renal tubular cells.