Non-classical functions of nuclear pore proteins in ciliopathy

Yan Chen; Yuan Zhang; Xiangyu Zhou

doi:10.3389/fmolb.2023.1278976

Non-classical functions of nuclear pore proteins in ciliopathy

Front Mol Biosci. 2023 Oct 16:10:1278976. doi: 10.3389/fmolb.2023.1278976. eCollection 2023.

Authors

Yan Chen¹, Yuan Zhang², Xiangyu Zhou¹

Affiliations

¹ Obstetrics and Gynecology Hospital of Fudan University, Fudan University Shanghai Medical College, Shanghai, China.
² Department of Assisted Reproduction, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.

Abstract

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, Nup188, Nup93 or Nup205 knockdown results in cilia loss, impacting cardiac left-right patterning in models and cell lines. Genetic variants of Nup205 and Nup188 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.

Keywords: NEK3; Nup188; Nup205; cilia; ciliopathy; left-right patterning; nuclear pore proteins; nucleoporins.

Publication types

Review

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. We acknowledge support from the National Natural Science Foundation of China (82171845, 81870285), National Key Research and Development Project (2018YFA0801300), and Shanghai Rising-Star Program (18QA1403500).