ARF4

Cilia effects upon perturbation of ARF4

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Shorter cilia

Overexpression effect:

No effect

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-2.92) 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:

abnormal embryo size, embryonic growth retardation, embryonic lethality prior to tooth bud stage, increased spleen weight, enlarged spleen, preweaning lethality, complete penetrance, abnormal spleen morphology

Subcellular localization

cilia associated gene, cytosol, endosome

Functional category

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

Function

Involved in ciliary targeting of rhodopsin and other proteins with VxPx motif (19153612). Targets proteins to cilia in association with ASAP1, RAB11 and RAB8 (22983554). Dispensable for ciliogenesis. Expression of dominant negative Arf4 reduced the percent of ciliated cells (Figure S1B) and ciliary length (Figure S1C). Surprisingly, over-expression of any Arf4 constructs completely inhibited CTS trafficking to the cilium (PMID: 24586199). Expression of dominant negative Arf4 reduced the percent of ciliated cells (Figure S1B) and ciliary length (Figure S1C). Surprisingly, over-expression of any Arf4 constructs completely inhibited CTS trafficking to the cilium (Figure S1D). These data indicate that increases in Arf4 levels prevent ciliary trafficking of the CTS possibly by sequestering it in the cytoplasm.

Model organism evidence