title: Amino- and carboxyl-terminal domains of Filamin-A interact with CRMP1 to mediate Sema3A signalling.
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.
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Nakamura
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kumeta
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hida
authors.affiliation: 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.
authors.forename: Toshinari
authors.initials: T
authors.lastname: Isono
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nakayama
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Kuramata-Matsuoka
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Yamashita
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Uchida
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ogura
authors.affiliation: Department of Physiology, Tokyo Women's Medical University School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Gengyo-Ando
authors.affiliation: Department of Physiology, Tokyo Women's Medical University School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Mitani
authors.affiliation: Division of Electrical and Computer Engineering, Yokohama National University, 79-1 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogino
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D064448:Filamins / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D017208:Rats, Wistar; D040121:Semaphorin-3A / Q000378:metabolism; D000098855:Collapsin Response Mediator Protein 1
chemical_list: D000199:Actins; D029742:Caenorhabditis elegans Proteins; C000604107:FLN-1 protein, C elegans; D064448:Filamins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D040121:Semaphorin-3A; D000098855:Collapsin Response Mediator Protein 1; C078652:unc-33 protein, C elegans