2. Academic Validation
  3. Amino- and carboxyl-terminal domains of Filamin-A interact with CRMP1 to mediate Sema3A signalling

Amino- and carboxyl-terminal domains of Filamin-A interact with CRMP1 to mediate Sema3A signalling

  • Nat Commun. 2014 Oct 31;5:5325. doi: 10.1038/ncomms6325.
Fumio Nakamura 1,  Kosuke Kumeta 1,  Tomonobu Hida 1,  Toshinari Isono 2,  Yuichi Nakayama 1,  Emiko Kuramata-Matsuoka 1,  Naoya Yamashita 1,  Yutaka Uchida 1,  Ken-ichi Ogura 1,  Keiko Gengyo-Ando 3,  Shohei Mitani 3,  Toshio Ogino 4,  Yoshio Goshima 1
Affiliations

Affiliations

  • 1 Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
  • 2 1] Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan [2] Division of Electrical and Computer Engineering, Yokohama National University, 79-1 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan.
  • 3 Department of Physiology, Tokyo Women's Medical University School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
  • 4 Division of Electrical and Computer Engineering, Yokohama National University, 79-1 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan.
PMID: 25358863 DOI: 10.1038/ncomms6325
Abstract

Reorganization of the actin Cytoskeleton is an early cellular response to various extracellular signals. Sema3A, a repulsive axon guidance molecule, induces the reorganization of actin Cytoskeleton in the growth cones. Collapsin response mediator protein 1 (CRMP1) mediates the intracellular Sema3A signalling through its Ser522 phosphorylation. Here we show that UNC-33, CRMP1 C. elegans homologue, interacts with FLN-1, an actin-binding Filamin-A orthologue. In nematodes, this interaction participates in the projection of DD/VD motor neurons. CRMP1 binds both the actin-binding domain and the last immunoglobulin-like repeat of Filamin-A. The alanine mutants of Filamin-A or CRMP1 in their interacting residues suppress the Sema3A repulsion in neurons. Conversely, a phosphor-mimicking mutant CRMP1(Ser522Asp) enhances the Sema3A response. Atomic-force microscopy analysis reveals that the V-shaped Filamin-A changes to a condensed form with CRMP1(Ser522Asp). CRMP1(Ser522Asp) weakens the F-actin gelation crosslinked by Filamin-A. Thus, phosphorylated CRMP1 may remove Filamin-A from the actin Cytoskeleton to facilitate its remodelling.

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