Wu Chuanyue
Department of Pathology, University of Pittsburgh, 707B Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
J Cell Sci. 2005 Feb 15;118(Pt 4):659-64. doi: 10.1242/jcs.01639.
Links between the plasma membrane and the actin cytoskeleton are essential for maintaining tissue integrity and for controlling cell morphology and behavior. Studies over the past several decades have identified dozens of components of such junctions. One of the most recently identified is migfilin, a widely expressed protein consisting of an N-terminal filamin-binding domain, a central proline-rich domain and three C-terminal LIM domains. Migfilin is recruited to cell-matrix contacts in response to adhesion and colocalizes with beta-catenin at cell-cell junctions in epithelial and endothelial cells. Migfilin also travels from the cytoplasm into the nucleus, a process that is regulated by RNA splicing and calcium signaling. Through interactions with multiple binding partners, including Mig-2, filamin and VASP, migfilin links the cell adhesion structures to the actin cytoskeleton. It regulates actin remodeling, cell morphology and motility. In nuclei, migfilin interacts with the cardiac transcriptional factor CSX/NKX2-5 and promotes cardiomyocyte differentiation. It probably functions as a key regulator both at cell adhesion sites and nuclei, coordinating multiple cellular processes, and is implicated in the pathogenesis of several human diseases.
质膜与肌动蛋白细胞骨架之间的联系对于维持组织完整性以及控制细胞形态和行为至关重要。过去几十年的研究已经确定了这类连接的数十种组成成分。最近发现的一种是迁移丝蛋白，它是一种广泛表达的蛋白质，由一个N端细丝蛋白结合结构域、一个富含脯氨酸的中央结构域和三个C端LIM结构域组成。迁移丝蛋白在黏附作用下被招募到细胞与基质的接触部位，并在上皮细胞和内皮细胞的细胞间连接处与β-连环蛋白共定位。迁移丝蛋白还从细胞质进入细胞核，这一过程受RNA剪接和钙信号调节。通过与包括Mig-2、细丝蛋白和VASP在内的多个结合伴侣相互作用，迁移丝蛋白将细胞黏附结构与肌动蛋白细胞骨架连接起来。它调节肌动蛋白重塑、细胞形态和运动性。在细胞核中，迁移丝蛋白与心脏转录因子CSX/NKX2-5相互作用并促进心肌细胞分化。它可能在细胞黏附位点和细胞核中均作为关键调节因子发挥作用，协调多种细胞过程，并且与几种人类疾病的发病机制有关。
