Interaction of CRMP1 and Filamin-A regulates F-actin-cytoskeleton.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24500443
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Yokohama City University
• Principal Investigator: NAKAMURA Fumio 横浜市立大学, 医学部, 准教授 (10262023)
• Co-Investigator(Kenkyū-buntansha): ARITA Kyohei 横浜市立大学, 生命ナノシステム科学研究科, 准教授 (40549648) ; YAMASHITA Naoya 横浜市立大学, 医学研究科, 客員講師 (40508793) ; HASHIMOTO Hiroshi 静岡県立大学, 薬学部, 教授 (40336590)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 神経回路形成 / 細胞骨格 / アクチン / セマフォリン / Sema3A / CRMP1 / Filamin-A / リン酸化

Outline of Final Research Achievements

Sema3A, an axon guidance molecule, repels neurite outgrowth. This action accompanies the collapse of actin-cytoskeleton in the neuronal growth cones. We found that CRMP1, an intracellular mediator for Sema3A-signaling, interacts with Filamin-A, an actin binding protein. In C. elegans, Filamin-1 (Filamin-A homologue) is involved in DD/VD motoneuron guidance with UNC-33 (CRMP1 homologue). CRMP1 binds N- and C-termini of Filamin-A and alters its ternary structure. We determined the interaction residues in Filamin-A and CRMP1. Overexpression of the point-mutants of those residues in cultured neurons interferes Sema3A-response. Sema3A induces phosphorylation of CRMP1. A phospho-mimicking mutant of CRMP1 binds Filamin-A with higher affinity than wildtype. The phospho-mimicking CRMP1 interferes the actin cytoskeleton weaved with F-actin and Filamin-A. These results suggest that phosphorylated CRMP1 removes Filamin-A from actin-cytoskeleton in turn to bring the collapse in Sema3A-signaling.

Free Research Field

神経生物学