Importin α regulates ciliogenesis and cilia length with implications for Xenopus nephrogenesis.

Abstract

Cilia are microtubule-based organelles essential for a wide range of biological processes ranging from facilitating fluid flow to transducing developmental and growth signals. Defects in cilia structure or function can lead to ciliopathies. Ciliogenesis and cilia length regulation depend on protein transport to the ciliary base, but the underlying molecular mechanisms remain unclear. Here we identify that the nuclear adapter protein, importin α, has conserved localization in human epithelial primary cilia and Xenopus laevis (X. laevis) epidermal multiciliated cells. Importin α regulates both ciliogenesis and cilia length maintenance, dependent on its localization to the membrane via palmitoylation or in the cytoplasm when not palmitoylated. In addition, we identify key ciliary proteins, CEP164 and ARL13B, as candidate binding partners of importin α through their NLS sequence and the requirement of this binding interaction for proper ciliogenesis and cilia length. Disruption of importin α palmitoylation in X. laevis causes defects in nephrogenesis which is rescued by forced membrane localization of importin α. These findings reveal a previously unrecognized role for importin α in cilia biology and advances understanding of congenital kidney diseases.