A novel mechanism that controls frequency and stability of lamellipodium formation

点击翻译按钮获取中文摘要

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.