Rust Marco B, Khudayberdiev Sharof, Pelucchi Silvia, Marcello Elena
Molecular Neurobiology Group, Institute of Physiological Chemistry, University of Marburg, Marburg, Germany.
DFG Research Training Group, Membrane Plasticity in Tissue Development and Remodeling, GRK 2213, University of Marburg, Marburg, Germany.
Front Cell Dev Biol. 2020 Sep 24;8:586631. doi: 10.3389/fcell.2020.586631. eCollection 2020.
Cyclase-associated protein (CAP) has been discovered three decades ago in budding yeast as a protein that associates with the cyclic adenosine monophosphate (cAMP)-producing adenylyl cyclase and that suppresses a hyperactive RAS2 variant. Since that time, CAP has been identified in all eukaryotic species examined and it became evident that the activity in RAS-cAMP signaling is restricted to a limited number of species. Instead, its actin binding activity is conserved among eukaryotes and actin cytoskeleton regulation emerged as its primary function. However, for many years, the molecular functions as well as the developmental and physiological relevance of CAP remained unknown. In the present article, we will compile important recent progress on its molecular functions that identified CAP as a novel key regulator of actin dynamics, i.e., the spatiotemporally controlled assembly and disassembly of actin filaments (F-actin). These studies unraveled a cooperation with ADF/Cofilin and Twinfilin in F-actin disassembly, a nucleotide exchange activity on globular actin monomers (G-actin) that is required for F-actin assembly and an inhibitory function towards the F-actin assembly factor INF2. Moreover, by focusing on selected model organisms, we will review current literature on its developmental and physiological functions, and we will present studies implicating CAP in human pathologies. Together, this review article summarizes and discusses recent achievements in understanding the molecular, developmental and physiological functions of CAP, which led this protein emerge as a novel CAPt'n of actin dynamics.
环化酶相关蛋白（CAP）于三十年前在出芽酵母中被发现，它是一种与产生环磷酸腺苷（cAMP）的腺苷酸环化酶相关联的蛋白质，并且能够抑制一种活性过高的RAS2变体。从那时起，在所有已检测的真核生物物种中都鉴定出了CAP，并且很明显，其在RAS - cAMP信号传导中的活性仅限于少数物种。相反，它的肌动蛋白结合活性在真核生物中是保守的，并且肌动蛋白细胞骨架调节已成为其主要功能。然而，多年来，CAP的分子功能以及其在发育和生理方面的相关性仍然未知。在本文中，我们将汇总有关其分子功能的重要最新进展，这些进展将CAP鉴定为肌动蛋白动力学的新型关键调节因子，即肌动蛋白丝（F - 肌动蛋白）的时空控制组装和解聚。这些研究揭示了它在F - 肌动蛋白解聚中与ADF / 丝切蛋白和双丝蛋白的合作，在F - 肌动蛋白组装中所需的球状肌动蛋白单体（G - 肌动蛋白）上的核苷酸交换活性以及对F - 肌动蛋白组装因子INF2的抑制功能。此外，通过关注选定的模式生物，我们将综述当前关于其发育和生理功能的文献，并展示涉及CAP在人类病理学中的研究。总之，这篇综述文章总结并讨论了在理解CAP的分子、发育和生理功能方面的最新成就，这些成就使这种蛋白质成为肌动蛋白动力学的新型“船长”。
