Murk Kai, Ornaghi Marta, Schiweck Juliane
Institute of Biochemistry, Charité Universitätsmedizin Berlin, Berlin, Germany.
Front Cell Dev Biol. 2021 Aug 12;9:681122. doi: 10.3389/fcell.2021.681122. eCollection 2021.
Profilins are small actin binding proteins, which are structurally conserved throughout evolution. They are probably best known to promote and direct actin polymerization. However, they also participate in numerous cell biological processes beyond the roles typically ascribed to the actin cytoskeleton. Moreover, most complex organisms express several profilin isoforms. Their cellular functions are far from being understood, whereas a growing number of publications indicate that profilin isoforms are involved in the pathogenesis of various diseases. In this review, we will provide an overview of the profilin family and "typical" profilin properties including the control of actin dynamics. We will then discuss the profilin isoforms of higher animals in detail. In terms of cellular functions, we will focus on the role of Profilin 1 (PFN1) and Profilin 2a (PFN2a), which are co-expressed in the central nervous system. Finally, we will discuss recent findings that link PFN1 and PFN2a to neurological diseases, such as amyotrophic lateral sclerosis (ALS), Fragile X syndrome (FXS), Huntington's disease and spinal muscular atrophy (SMA).
丝切蛋白是一类小分子肌动蛋白结合蛋白，其结构在整个进化过程中保持保守。它们可能最为人所知的是促进和指导肌动蛋白聚合。然而，它们还参与了许多超出通常归因于肌动蛋白细胞骨架作用的细胞生物学过程。此外，大多数复杂生物表达多种丝切蛋白异构体。它们的细胞功能远未被了解，而越来越多的出版物表明丝切蛋白异构体参与了各种疾病的发病机制。在本综述中，我们将概述丝切蛋白家族以及“典型”丝切蛋白特性，包括对肌动蛋白动力学的控制。然后我们将详细讨论高等动物的丝切蛋白异构体。在细胞功能方面，我们将重点关注在中枢神经系统中共同表达的丝切蛋白1（PFN1）和丝切蛋白2a（PFN2a）的作用。最后，我们将讨论将PFN1和PFN2a与神经疾病（如肌萎缩侧索硬化症（ALS）、脆性X综合征（FXS）、亨廷顿舞蹈症和脊髓性肌萎缩症（SMA））联系起来的最新研究发现。
