ABCC4

Cilia effects upon perturbation of ABCC4

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (4 screens)

• Kim2016: Not Reported
• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-3.30) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Ciliopathy associations

• Preaxial Polydactyly

Subcellular localization

cilia associated gene

Functional category

• Ciliary assembly/disassembly
• Metabolism
• Signaling (Hedgehog, GPCRs, ion channels)
• Cilia length regulation

Function

Also known as leakytail. ATP- binding cassette transporter which transports prostaglandin E2 and other molecules across cellular membranes. Mutations in ABCC4 cause ciliogenesis defects. ABCC4-mediated PGE2 sig lling acts through a ciliary G-protein-coupled receptor, EP4, to upregulate cAMP synthesis and increase anterograde IFT, thereby promoting ciliogenesis ( 25173977). Zebrafish abcc4 mutants exhibited loss of connecting cilia and outer segment in photoreceptor cells, leading to mislocalization of opsins in the cell bodies of photoreceptors ( 30685088). Specific missense associated with polydactyly in pigs ( 32228435). We observed that depletion of ABCC4 or EP4 in hRPE1 cells caused a reduction of ciliaformation and elongation when compared with use of the control siRNA (Fig. 7a, b, c). Bothcilia length and percentages of ciliated cells were significantly reduced in ABCC4 or EP4 depleted cells (Fig. 7g. h). Addition of exogenous PGE2 increased both cilia length and percentages of ciliated cells in control cells but not in EP4-depleted cells (Fig. 7a, d, g, h), indicating that EP4 acts downstream of PGE2 signaling during ciliogenesis. ( 25173977)