Sutton, P. J. | Search bioRxiv

bioRxiv2025

A Role for Importin α in Ciliogenesis and Cilia Length Regulation during Nephrogenesis

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.

cell biology↗

bioRxiv2024

Palmitoylated Importin α Regulates Mitotic Spindle Orientation Through Interaction with NuMA

Regulation of cell division orientation is a fundamental process critical to differentiation and tissue homeostasis. Microtubules emanating from the mitotic spindle pole bind a conserved complex of proteins at the cell cortex which orients the spindle and ultimately the cell division plane. Control of spindle orientation is of particular importance in developing tissues, such as the developing brain. Misorientation of the mitotic spindle and thus subsequent division plane misalignment can contribute to improper segregation of cell fate determinants in developing neuroblasts, leading to a rare neurological disorder known as microcephaly. We demonstrate that the nuclear transport protein importin , when palmitoylated, plays a critical role in mitotic spindle orientation through localizing factors, such as NuMA, to the cell cortex. We also observe craniofacial developmental defects in Xenopus laevis when importin palmitoylation is abrogated, including smaller head and brains, a hallmark of spindle misorientation and microcephaly. These findings characterize not only a role for importin in spindle orientation, but also a broader role for importin palmitoylation which has significance for many cellular processes.

cell biology↗