Multifaceted roles of nonmuscle myosin II in cell adhesion and migration

II类(常规)肌球蛋白是肌动蛋白依赖的马达，能够独特地聚合成 两极细丝，这使它们能够驱动细胞收缩。非肌肉肌球蛋白II(NMII)是 在动物细胞中普遍表达，在那里执行包括细胞黏附在内的许多机械任务 和迁移，以及细胞内可收缩细胞骨架的整体组织。与大型和 由肌肉特异性肌球蛋白II平行序列形成的稳定的双极细丝，NMII细丝细小而高度 活力四射。通过在聚合状态和单体状态之间不断循环，NMII可以适应变化 细胞需要并帮助细胞选择适当的迁移模式。我们最近发现了两个新的 NMII动力学方面：(1)NMII平行对映体共聚合成杂化双极丝和(2)官能化 活化的，但未聚合的NMII单体的意义，以前被认为只是 NMII激活的瞬时中间产物。我们的目标是确定这些新的 NMII动态的各个方面。具体地说，我们将检验我们的假设：(1)NMII对映体的共聚 是在细胞内建立收缩系统的极化组织从而促进 细胞定向迁移和(2)激活的NMII单体调节细胞-基质黏附的动态。一个 这两个模型的关键要素都是在重链水平上调节NMII，它调节 混合双极长丝，并产生活化的NMII单体。我们致力于以下具体目标：(1) NMII共聚在收缩系统组织和细胞迁移中的作用；(2)重链- NMII周转对细胞骨架极化和细胞迁移的依赖机制；以及(3) 在细胞-基质黏附的动力学中激活NMII单体。

Class II (conventional) myosins are actin-dependent motors that are uniquely able to polymerize into bipolar filaments, which makes them capable of driving cell contraction. Nonmuscle myosin II (NMII) is ubiquitously expressed in animal cells, where it executes numerous mechanical tasks including cell adhesion and migration, as well as overall organization of the contractile cytoskeleton in the cell. In contrast to large and stable bipolar filaments formed by muscle-specific myosin II paralogs, NMII filaments are small and highly dynamic. By constantly cycling between polymeric and monomeric states, NMII can accommodate changing cellular needs and help the cell to choose an appropriate mode of migration. We recently discovered two new aspects of NMII dynamics: (1) copolymerization of NMII paralogs into hybrid bipolar filaments and (2) functional significance of activated, but unpolymerized NMII monomers that were previously considered to be only transient intermediates of NMII activation. Our goal is to determine physiological significance of these new aspects of NMII dynamics. Specifically, we will test our hypotheses that (1) copolymerization of NMII paralogs is a key mechanism to establish polarized organization of the contractile system in cells and thus promote directional cell migration and that (2) activated NMII monomers regulate dynamics of cell-matrix adhesions. A key element of both models is regulation of NMII at the heavy chain level, which modulates composition of hybrid bipolar filaments and generates activated NMII monomers. We address the following specific aims: (1) Roles of NMII copolymerization for contractile system organization and cell migration; (2) Roles of heavy chain- dependent mechanisms of NMII turnover for cytoskeleton polarization and cell migration; and (3) Roles of activated NMII monomers in dynamics of cell-matrix adhesions.