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.