AUTHOR=Chen Yan , Zhang Yuan , Zhou Xiangyu 

TITLE=Non-classical functions of nuclear pore proteins in ciliopathy

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1278976

DOI=10.3389/fmolb.2023.1278976

ISSN=2296-889X

ABSTRACT=<p>Nucleoporins (NUPs) constitute integral nuclear pore protein (NPC) elements. Although traditional NUP functions have been extensively researched, evidence of additional vital non-NPC roles, referred to herein as non-classical NUP functions, is also emerging. Several NUPs localise at the ciliary base. Indeed, <italic>Nup188</italic>, <italic>Nup93</italic> or <italic>Nup205</italic> knockdown results in cilia loss, impacting cardiac left–right patterning in models and cell lines. Genetic variants of <italic>Nup205</italic> and <italic>Nup188</italic> have been identified in patients with congenital heart disease and situs inversus totalis or heterotaxy, a prevalent human ciliopathy. These findings link non-classical NUP functions to human diseases. This mini-review summarises pivotal NUP interactions with NIMA-related kinases or nephronophthisis proteins that regulate ciliary function and explores other NUPs potentially implicated in cilia-related disorders. Overall, elucidating the non-classical roles of NUPs will enhance comprehension of ciliopathy aetiology.</p>