Geisbrecht Erika R, Montell Denise J
Department of Biological Chemistry, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA.
Nat Cell Biol. 2002 Aug;4(8):616-20. doi: 10.1038/ncb830.
Myosin VI (MyoVI) is a pointed-end-directed, actin-based motor protein, and mutations in the gene result in disorganization of hair cell stereocilia and cause deafness in mice. MyoVI also localizes to the leading edges of growth-factor-stimulated fibroblast cells and has been suggested to be involved in cell motility. There has been no direct test of this hypothesis, however. Drosophila melanogaster MyoVI is expressed in a small group of migratory follicle cells, known as border cells. Here we show that depletion of MyoVI specifically from border cells severely inhibited their migration. Similar to MyoVI, E-cadherin is required for border cell migration. We found that E-cadherin and Armadillo (Arm, Drosophila beta-catenin) protein levels were specifically reduced in cells lacking MyoVI, whereas other proteins were not. In addition, MyoVI protein levels were reduced in cells lacking DE-cadherin or Arm. MyoVI and Arm co-immunoprecipitated from ovarian protein extracts. These data suggest that MyoVI is required for border cell migration where it stabilizes E-cadherin and Arm. Mutations in MyoVIIA, another unconventional myosin protein, also lead to deafness, and MyoVIIA interacts with E-cadherin through a membrane protein called vezatin. Multiple biochemical mechanisms may exist, therefore, for cadherins to associate with diverse unconventional myosins that are required for normal stereocilium formation or maintenance.
肌球蛋白VI（MyoVI）是一种基于肌动蛋白的、指向尖端的运动蛋白，该基因的突变会导致毛细胞静纤毛紊乱，并在小鼠中引起耳聋。MyoVI也定位于生长因子刺激的成纤维细胞的前缘，有人认为它参与细胞运动。然而，尚未对这一假设进行直接测试。果蝇的MyoVI在一小群迁移的卵泡细胞（称为边缘细胞）中表达。在这里，我们表明，特异性地从边缘细胞中去除MyoVI会严重抑制它们的迁移。与MyoVI类似，E-钙黏蛋白是边缘细胞迁移所必需的。我们发现，在缺乏MyoVI的细胞中，E-钙黏蛋白和犰狳蛋白（Arm，果蝇β-连环蛋白）水平特异性降低，而其他蛋白则没有。此外，在缺乏DE-钙黏蛋白或Arm的细胞中，MyoVI蛋白水平降低。MyoVI和Arm从卵巢蛋白提取物中共免疫沉淀。这些数据表明，MyoVI是边缘细胞迁移所必需的，它在其中稳定E-钙黏蛋白和Arm。另一种非常规肌球蛋白蛋白MyoVIIA的突变也会导致耳聋，并且MyoVIIA通过一种称为vezatin的膜蛋白与E-钙黏蛋白相互作用。因此，可能存在多种生化机制，使钙黏蛋白与正常静纤毛形成或维持所需的多种非常规肌球蛋白相关联。
