CEP41, a ciliopathy-linked centrosomal protein, regulates microtubule assembly and cell division

Abstract

AbstractCentrosomal proteins play pivotal roles in orchestrating microtubule dynamics, and their dysregulation leads to various disorders, including cancer and ciliopathies. Understanding the multifaceted roles of centrosomal proteins is vital to comprehend their involvement in disease development. Here, we report novel cellular functions of CEP41, a centrosomal and ciliary protein implicated in Joubert syndrome, a neurodevelopmental ciliopathy. We show that CEP41 is an essential microtubule-associated protein with microtubule-stabilizing activity.In vitro, purified CEP41 binds to preformed microtubules, promotes microtubule nucleation, and suppresses microtubule disassembly. When overexpressed in cultured cells, CEP41 localizes to microtubules and promotes formation of stable microtubule bundles. Conversely, shRNA-mediated knockdown of CEP41 causes disassembly of the interphase microtubule network, emphasizing its role in microtubule organization. Using GFP-tagged deletion constructs, we demonstrate that CEP41’s association with microtubules relies on its conserved rhodanese homology domain and the N- terminal region. Furthermore, CEP41 depletion inhibits cell proliferation and induces G1 arrest, suggesting its potential role in cell cycle regulation. These insights into the cellular functions of CEP41 hold promise for unraveling the impact of its mutations in ciliopathies.SummaryA novel role of CEP41 as a microtubule-associated protein that promotes microtubule assembly and regulates cell cycle progression could offer insights into the development of ciliopathies.