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

Cilia are microtubule-based organelles that are 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-1 (encoded by KPNA2 in humans; hereafter importin α) has conserved localization in human epithelial primary cilia and Xenopus laevis epidermal multiciliated cells. We find that importin α regulates both ciliogenesis and cilia length maintenance in a way that is dependent on both its localization to the membrane via palmitoylation and its presence 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 nuclear localization sequence (NLS) 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 are 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.