A novel mechanism that controls frequency and stability of lamellipodium formation

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 12470002
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Fukui Medical University
• Principal Investigator: SATO Makoto Fukui Medical University, Faculty of Medicine, Professor, 医学部, 教授 (10222019)
• Co-Investigator(Kenkyū-buntansha): YAGI Hideshi Fukui Medical University, Faculty of Medicine, Research Associate, 医学部, 助手 (10303372) ; NAGANO Takashi Fukui Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (70272854)
• Project Period (FY): 2000 – 2002
• Keywords: actin / cell motility / cytoskeleton / lamellipodium / F-actin / Filamin / actin binding protein / calpain

Research Abstract

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.

Research Products

• [Publications] Nagano, T., Yoneda, T., Hatanaka, Y., Kubota, C., Murakami, F., Sato, M.: "Filamin A-interacting protein (FILIP) regulates cortical cell migration out of the ventricular zone"Nature Cell Biology. 4. 495-501 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nagano, T., Yoneda, T., Hatanaka, Y., Kubota, C., Murakami, F. and Sato, M.: "Filamin A-interacting protein (FILIP) regulates cortical cell migration out of the ventricular zone"Nature Cell Biology. 4(7). 495-501 (2002)
  • Description: 「研究成果報告書概要(欧文)」より