AKAP12

Cilia effects upon perturbation of AKAP12

Cilia number / % ciliated:

Unknown

Loss-of-function effect:

Shorter cilia

Overexpression effect:

Longer cilia

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-3.35) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Subcellular localization

cilia associated gene

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Actin & cytoskeleton regulation
• Cell migration & adhesion
• Signaling (Hedgehog, GPCRs, ion channels)
• Transcription regulation
• Cilia length regulation

Function

Ectopic expression of Akap12 in renal epithelia results in abnormally long primary cilia similar to that observed in Notch-signaling-deficient epithelia. Both loss of Notch signaling and elevated Akap12 expression disrupt the ability of renal epithelial cells to form spherical structures with a single lumen when grown embedded in matrix. Interestingly, Akap12 can inhibit Notch signaling mediated transcription, which likely explains how both loss of Notch signaling and ectopic expression of Akap12 result in similar renal epithelial abnormalities. We conclude that Notch signaling regulates Akap12 expression while also ensuring normal primary cilia length and renal epithelial morphogenesis, and suggest that one aspect of diseases associated with defective Notch signaling, such as Alagille syndrome, maybe mechanistically related to ciliopathies(32474964).