A Role for Importin α in Ciliogenesis and Cilia Length Regulation during Nephrogenesis
Mosqueda, N.; Sutton, P. J.; Brownlee, C. W.
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Cilia are evolutionary conserved microtubule-based organelles involved in many biological processes. Motile cilia facilitate fluid flow, while primary cilia transduce developmental and growth signals. Defects in cilia structure or function can lead to a spectrum of ciliopathies. Ciliogenesis and length regulation depend on protein transport to the ciliary base, but the molecular mechanisms remain unclear. We demonstrate that the nuclear transport protein, importin , when membrane-localized via palmitoylation, or non-palmitoylated in the cytoplasm, localizes to the base or lumen of primary and motile cilia. There we find it is required to initiate ciliogenesis and maintain proper cilia length. We found importin binds Cep164, Cep78, and Arl13b, proteins essential for ciliogenesis and length maintenance. Disrupting importin palmitoylation in Xenopus laevis lead to abnormal kidney morphology and reduced renal primary cilia. These findings reveal a novel pathway through which importin contributes to ciliogenesis and advance understanding of ciliopathy etiology.
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