Epb41l5 interacts with IQCB1 and regulates ciliary function in zebrafish embryos

Erythrocyte protein band 4.1 like 5 (Epb41l5) is an adaptor protein beneath the plasma membrane that functions to control epithelial morphogenesis. Here we report a previously uncharacterized role of Epb41l5 in controlling ciliary function. We found that Epb41l5 forms a complex with IQCB1/NPHP5, a ciliopathy gene. Epb415 overexpression reduced IQCB1 localization at the ciliary base in cultured epithelial cells. Conversely, epb41l5 knockdown increased IQCB1 localization at the ciliary base. epb41l5-deficient zebrafish embryos or embryos expressing the C-terminally modified forms of Epb41l5 developed cilia with reduced motility and exhibited left-right patterning defects, an outcome of abnormal ciliary function. We observed genetic synergy between epb41l5 and iqcb1. Finally, Epb41l5 decreased IQCB1 interaction with Cep290, another ciliopathy gene and a component of the ciliary base and the centrosome. Together, these observations suggest that Epb41l5 regulates the composition of the ciliary base and the centrosome through IQCB1 and Cep290.