Schmidt Kristopher L, Marcus-Gueret Nancy, Adeleye Adetayo, Webber Jordan, Baillie David, Stringham Eve G
Department of Biology, Trinity Western University, Langley, BC V2Y 1Y1, Canada.
Development. 2009 Feb;136(4):563-74. doi: 10.1242/dev.016816.
The shape changes that are required to position a cell to migrate or grow out in a particular direction involve a coordinated reorganization of the actin cytoskeleton. Although it is known that the ARP2/3 complex nucleates actin filament assembly, exactly how the information from guidance cues is integrated to elicit ARP2/3-mediated remodeling during outgrowth remains vague. Previous studies have shown that C. elegans UNC-53 and its vertebrate homolog NAV (Neuronal Navigators) are required for the migration of cells and neuronal processes. We have identified ABI-1 as a novel molecular partner of UNC-53/NAV2 and have found that a restricted calponin homology (CH) domain of UNC-53 is sufficient to bind ABI-1. ABI-1 and UNC-53 have an overlapping expression pattern, and display similar cell migration phenotypes in the excretory cell, and in mechanosensory and motoneurons. Migration defects were also observed after RNAi of proteins known to function with abi-1 in actin dynamics, including nck-1, wve-1 and arx-2. We propose that UNC-53/NAV2, through its CH domain, acts as a scaffold that links ABI-1 to the ARP2/3 complex to regulate actin cytoskeleton remodeling.
细胞要在特定方向上迁移或生长，其形状变化需要肌动蛋白细胞骨架进行协调重组。虽然已知ARP2/3复合物能促使肌动蛋白丝组装成核，但在细胞生长过程中，引导信号的信息究竟如何整合以引发ARP2/3介导的重塑仍不清楚。先前的研究表明，秀丽隐杆线虫的UNC-53及其脊椎动物同源物NAV（神经元导航蛋白）是细胞和神经突起迁移所必需的。我们已确定ABI-1是UNC-53/NAV2的一种新的分子伴侣，并发现UNC-53一个有限的钙调蛋白同源（CH）结构域足以结合ABI-1。ABI-1和UNC-53具有重叠的表达模式，并且在排泄细胞、机械感觉神经元和运动神经元中表现出相似的细胞迁移表型。在用已知在肌动蛋白动力学中与abi-1共同发挥作用的蛋白质（包括nck-1、wve-1和arx-2）进行RNA干扰后，也观察到了迁移缺陷。我们提出，UNC-53/NAV2通过其CH结构域，作为一个支架，将ABI-1与ARP2/3复合物连接起来，以调节肌动蛋白细胞骨架的重塑。
