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

Fumio Nakamura; Kosuke Kumeta; Tomonobu Hida; Toshinari Isono; Yuichi Nakayama; Emiko Kuramata-Matsuoka; Naoya Yamashita; Yutaka Uchida; Ken Ichi Ogura; Keiko Gengyo-Ando; Shohei Mitani; Toshio Ogino; Yoshio Goshima

doi:10.1038/ncomms6325

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

Fumio Nakamura, Kosuke Kumeta, Tomonobu Hida, Toshinari Isono, Yuichi Nakayama, Emiko Kuramata-Matsuoka, Naoya Yamashita, Yutaka Uchida, Ken Ichi Ogura, Keiko Gengyo-Ando, Shohei Mitani, Toshio Ogino, Yoshio Goshima

Research output: Contribution to journal › Article › peer-review

35 Citations (Scopus)

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.

Original language	English
Article number	5325
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6325
Publication status	Published - 2014
Externally published	Yes

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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10.1038/ncomms6325

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@article{34ae1a3f53e04948aab9e896b78d050e,

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.",

author = "Fumio Nakamura and Kosuke Kumeta and Tomonobu Hida and Toshinari Isono and Yuichi Nakayama and Emiko Kuramata-Matsuoka and Naoya Yamashita and Yutaka Uchida and Ogura, {Ken Ichi} and Keiko Gengyo-Ando and Shohei Mitani and Toshio Ogino and Yoshio Goshima",

note = "Funding Information: We thank Robert Barstead for the two-hybrid cDNA library, Roger Y. Tsien for the mRFP clone, Andrew Fire and Daisuke Tsuboi for the C. elegans expression vectors and Takahiro Nagase for human-Filamin-A cDNA. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). We thank Joseph G Culotti and Sin Takagi for providing mab-20(ev574) and plx-2(tm729), respectively. We also thank Takako Okada, Hidenori Muraoka and Masami Obara for their excellent technical assistance, and Sandy Cheng and Lisa Bond for their critical reading of the manuscript. This work is supported by Grants from Grant-in-Aid for Scientific Research (C) form Japan Society for the Promotion of Science (JSPS) No. 24500443 to F.N.; from Grant-in-aid for Scientific Research on Priority Areas No. 17082006, from Targeted Proteins Research Program of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and from the fund for Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems from the MEXT to Y.G.",

year = "2014",

doi = "10.1038/ncomms6325",

language = "English",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Amino- and carboxyl-terminal domains of Filamin-A interact with CRMP1 to mediate Sema3A signalling

AU - Nakamura, Fumio

AU - Kumeta, Kosuke

AU - Hida, Tomonobu

AU - Isono, Toshinari

AU - Nakayama, Yuichi

AU - Kuramata-Matsuoka, Emiko

AU - Yamashita, Naoya

AU - Uchida, Yutaka

AU - Ogura, Ken Ichi

AU - Gengyo-Ando, Keiko

AU - Mitani, Shohei

AU - Ogino, Toshio

AU - Goshima, Yoshio

N1 - Funding Information: We thank Robert Barstead for the two-hybrid cDNA library, Roger Y. Tsien for the mRFP clone, Andrew Fire and Daisuke Tsuboi for the C. elegans expression vectors and Takahiro Nagase for human-Filamin-A cDNA. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). We thank Joseph G Culotti and Sin Takagi for providing mab-20(ev574) and plx-2(tm729), respectively. We also thank Takako Okada, Hidenori Muraoka and Masami Obara for their excellent technical assistance, and Sandy Cheng and Lisa Bond for their critical reading of the manuscript. This work is supported by Grants from Grant-in-Aid for Scientific Research (C) form Japan Society for the Promotion of Science (JSPS) No. 24500443 to F.N.; from Grant-in-aid for Scientific Research on Priority Areas No. 17082006, from Targeted Proteins Research Program of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and from the fund for Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems from the MEXT to Y.G.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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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U2 - 10.1038/ncomms6325

DO - 10.1038/ncomms6325

M3 - Article

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SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

M1 - 5325

ER -

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

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