A novel mechanism that controls frequency and stability of lamellipodium formation

细胞运动对于发育、组织形成甚至对于某些疾病的进展（包括癌细胞的转移和动脉粥样硬化的进展）起着至关重要的作用。对于细胞运动，板状伪足的形成是至关重要的，许多肌动蛋白结合蛋白调节板状伪足活动的动力学。已经证明，破坏细丝蛋白A抑制板状伪足的形成并杀死细胞迁移的活性。在这里，我们表明，一种新的蛋白质FILIP调节细胞迁移，通过与肌动蛋白结合蛋白，细丝蛋白A的直接相互作用，我们首先确定和克隆两个FILIPs，这两个是不同的，只有在他们的5'末端彼此。推导的氨基酸序列表明，S-FILIP（短型FILIP）在其N-末端缺少L-FILIP（长型FILIP）的247个残基。这两种FILIPs抑制板状伪足形成和细胞运动性，并诱导细丝蛋白A降解体外。细丝蛋白A的这种降解被钙蛋白酶抑制剂抑制，表明钙蛋白酶或等效的钙蛋白酶敏感性蛋白酶参与了该过程。这些结果表明，FILIP通过细丝蛋白A-F作用轴起作用，为控制细胞迁移提供了一种新的机制。

Cell movement plays an essential role for development, tissue formation and even for the advance of some disease, including transfer of cancer cells and the progression of atheroscleosis. For cell movement, lamellipodium formation is crucial, and many actin-binding proteins modulate dynamics of lamellipodium activity. It has been demonstrated that disruption of Filamin A suppresses lamellipodium formation and kills the activity of cell migration. Here we show that a novel protein FILIP regulates cell migration through direct interaction with an actin-binding protein, Filamin A ; We first identified and cloned two FILIPs, both of which were different only in their 5' termini with each other. Their deduced amino acid sequences indicated that S-FILIP (short form FILIP) lacks 247 residues of L-FILIP (long form FILIP) at its N-terminus. Both FILIPs suppressed lamellipodium formation and cell motility and induces Filamin A degradation in vitro. This degradation of Filamin A was inhibited by calpain inhibitors, suggesting that calpain or an equivalent calpeptin-sensitive protease(s) are involved in this process. These results indicate that FILIP acts through the Filamin A-F-action axis to provide a novel mechanism for control of cell migration.