Division of Cancer Cell Research, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
J Biol Chem. 2010 Jul 2;285(27):21013-22. doi: 10.1074/jbc.M110.106443. Epub 2010 May 3.
Cell migration on an extracellular matrix (ECM) requires continuous formation and turnover of focal adhesions (FAs) along the direction of cell movement. However, our knowledge of the components of FAs and the mechanism of their regulation remains limited. Here, we identify ZF21, a member of a protein family characterized by the presence of a phosphatidylinositol 3-phosphate-binding FYVE domain, to be a new regulator of FAs and cell movement. Knockdown of ZF21 expression in cells increased the number of FAs and suppressed cell migration. Knockdown of ZF21 expression also led to a significant delay in FA disassembly following induction of synchronous disassembly of FAs by nocodazole treatment. ZF21 bound to focal adhesion kinase, localized to FAs, and was necessary for dephosphorylation of FAK at Tyr(397), which is important for disassembly of FAs. Thus, ZF21 represents a new component of FAs, mediates disassembly of FAs, and thereby regulates cell motility.
细胞在细胞外基质（ECM）上的迁移需要沿着细胞运动的方向不断形成和转换焦点黏附（FA）。然而，我们对 FA 的组成成分和其调控机制的了解仍然有限。在这里，我们鉴定出 ZF21，一种特征在于存在具有磷酸肌醇 3-磷酸结合 FYVE 结构域的蛋白质家族的成员，是 FA 和细胞运动的新调节剂。在细胞中敲低 ZF21 的表达会增加 FA 的数量并抑制细胞迁移。敲低 ZF21 的表达也会导致在通过诺考达唑处理诱导 FA 同步解聚后 FA 解聚的明显延迟。ZF21 与粘着斑激酶结合，定位于 FA，并需要 FAK 在 Tyr（397）上的去磷酸化，这对于 FA 的解聚很重要。因此，ZF21 代表 FA 的一个新组成部分，介导 FA 的解聚，从而调节细胞迁移。
