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 (previously known as NPHP5), a ciliopathy protein. Overexpression of EPB41L5 reduced IQCB1 localization at the ciliary base in cultured mammalian epithelial cells. Conversely, epb41l5 knockdown increased IQCB1 localization at the ciliary base. epb41l5-deficient zebrafish embryos or embryos expressing 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. Moreover, EPB41L5 decreased IQCB1 interaction with CEP290, another ciliopathy protein and a component of the ciliary base and centrosome. Together, these observations suggest that EPB41L5 regulates the composition of the ciliary base and centrosome through IQCB1 and CEP290.