Smart Karishma, Sharp David J
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA.
Microcures, Inc., Bronx, New York, USA.
Cytoskeleton (Hoboken). 2024 Feb-Mar;81(2-3):151-166. doi: 10.1002/cm.21799. Epub 2023 Oct 12.
The microtubule cytoskeleton is required for several crucial cellular processes, including chromosome segregation, cell polarity and orientation, and intracellular transport. These functions rely on microtubule stability and dynamics, which are regulated by microtubule-binding proteins (MTBPs). One such type of regulator is the microtubule-severing enzymes (MSEs), which are ATPases Associated with Diverse Cellular Activities (AAA+ ATPases). The most recently identified family are the fidgetins, which contain three members: fidgetin, fidgetin-like 1 (FL1), and fidgetin-like 2 (FL2). Of the three known MSE families, the fidgetins have the most diverse range of functions in the cell, spanning mitosis/meiosis, development, cell migration, DNA repair, and neuronal function. Furthermore, they offer intriguing novel therapeutic targets for cancer, cardiovascular disease, and wound healing. In the two decades since their first report, there has been great progress in our understanding of the fidgetins; however, there is still much left unknown about this unusual family. This review aims to consolidate the present body of knowledge of the fidgetin family of MSEs and to inspire deeper exploration into the fidgetins and the MSEs as a whole.
微管细胞骨架对于几个关键的细胞过程是必需的，包括染色体分离、细胞极性和方向以及细胞内运输。这些功能依赖于微管的稳定性和动态性，而微管的稳定性和动态性由微管结合蛋白（MTBPs）调节。其中一种调节因子是微管切断酶（MSEs），它们是与多种细胞活动相关的ATP酶（AAA + ATP酶）。最近发现的家族是fidgetin家族，它包含三个成员：fidgetin、fidgetin样蛋白1（FL1）和fidgetin样蛋白2（FL2）。在已知的三个MSE家族中，fidgetin家族在细胞中的功能最为多样，涵盖有丝分裂/减数分裂、发育、细胞迁移、DNA修复和神经元功能。此外，它们为癌症、心血管疾病和伤口愈合提供了引人入胜的新型治疗靶点。自首次报道以来的二十年里，我们对fidgetin家族的理解取得了很大进展；然而，对于这个不同寻常的家族仍有许多未知之处。这篇综述旨在整合目前关于MSEs的fidgetin家族的知识体系，并激发对fidgetin家族以及整个MSEs进行更深入的探索。
