Evolution and functional divergence of the Fidgetin family

The Fidgetin (FIGN) family, which comprises FIGN, Fidgetin-like 1 (FIGNL1), and Fidgetin-like 2 (FIGNL2), is a vital group of microtubule-severing proteins. These proteins feature a conserved AAA+ domain essential for ATPase activity and a hexameric assembly. This review provides an in-depth analysis of the evolution and functional divergence of the FIGN family members, highlighting their role in the dynamic organization of the cytoskeleton. We further explore their broader biological functions across various species, systems, and subcellular localization. Although the FIGN family is conserved, each member exhibits unique structural characteristics and functions that reflect their evolutionary adaptations. FIGNL1 is found across animal species, while FIGNL2 is specific to vertebrates, thereby indicating its more recent evolutionary origin. Moreover, synteny analysis has revealed that FIGN is located in a more conserved genomic region compared to FIGNL2, which has undergone substantial evolutionary changes. The expression patterns of the FIGN members also vary across organisms and tissues. For example, FIGNL2 shows a notably reduced expression in the mammalian nervous system compared to that in lower vertebrates. The FIGN family members have distinct roles in microtubule severing, cell division, and DNA repair. Specifically, FIGN is involved in cell division and neuronal regeneration, FIGNL1 in axonal growth and DNA repair, and FIGNL2 in cell migration and vascular development. Their involvement in these processes underscores their role as potential biomarkers for certain cancers as well as therapeutic targets for diseases affecting the nervous system and cardiovascular development. All these evolutionary insights and functional distinctions of the FIGN family offer a comprehensive framework for understanding cytoskeletal regulation and its implications in health and disease.