CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth

Takashi Nishimura; Yuko Fukata; Katsuhiro Kato; Tomoya Yamaguchi; Yoshiharu Matsuura; Hiroyuki Kamiguchi; Kozo Kaibuchi

doi:10.1038/ncb1039

CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth

Takashi Nishimura, Yuko Fukata, Katsuhiro Kato, Tomoya Yamaguchi, Yoshiharu Matsuura, Hiroyuki Kamiguchi, Kozo Kaibuchi

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

225 Citations (Scopus)

Abstract

Axon growth during neural development is highly dependent on both cytoskeletal re-organization and polarized membrane trafficking. Previously, we demonstrated that collapsin response mediator protein-2 (CRMP-2) is critical for specifying axon/dendrite fate and axon growth in cultured hippocampal neurons, possibly by interacting with tubulin heterodimers and promoting microtubule assembly. Here, we identify Numb as a CRMP-2-interacting protein. Numb has been shown to interact with α-adaptin and to be involved in endocytosis. We found that Numb was associated with L1, a neuronal cell adhesion molecule that is endocytosed and recycled at the growth cone, where CRMP-2 and Numb were colocalized. Furthermore, expression of dominant-negative CRMP-2 mutants or knockdown of CRMP-2 message with small-interfering (si) RNA inhibited endocytosis of L1 at axonal growth cones and suppressed axon growth. These results suggest that in addition to regulating microtubule assembly, CRMP-2 is involved in polarized Numb-mediated endocytosis of proteins such as L1.

Original language	English
Pages (from-to)	819-826
Number of pages	8
Journal	Nature Cell Biology
Volume	5
Issue number	9
DOIs	https://doi.org/10.1038/ncb1039
Publication status	Published - 01-09-2003
Externally published	Yes

All Science Journal Classification (ASJC) codes

Cell Biology

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10.1038/ncb1039

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@article{e81c50a529b64413ba0208adad6a8c8a,

title = "CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth",

abstract = "Axon growth during neural development is highly dependent on both cytoskeletal re-organization and polarized membrane trafficking. Previously, we demonstrated that collapsin response mediator protein-2 (CRMP-2) is critical for specifying axon/dendrite fate and axon growth in cultured hippocampal neurons, possibly by interacting with tubulin heterodimers and promoting microtubule assembly. Here, we identify Numb as a CRMP-2-interacting protein. Numb has been shown to interact with α-adaptin and to be involved in endocytosis. We found that Numb was associated with L1, a neuronal cell adhesion molecule that is endocytosed and recycled at the growth cone, where CRMP-2 and Numb were colocalized. Furthermore, expression of dominant-negative CRMP-2 mutants or knockdown of CRMP-2 message with small-interfering (si) RNA inhibited endocytosis of L1 at axonal growth cones and suppressed axon growth. These results suggest that in addition to regulating microtubule assembly, CRMP-2 is involved in polarized Numb-mediated endocytosis of proteins such as L1.",

author = "Takashi Nishimura and Yuko Fukata and Katsuhiro Kato and Tomoya Yamaguchi and Yoshiharu Matsuura and Hiroyuki Kamiguchi and Kozo Kaibuchi",

note = "Funding Information: We thank Y. Gu, Y. Ihara, A. Craig, M. Nakafuku, A. Tokunaga, H. Okano and V. Lemmon for their kind gifts of materials. We also thank M. Amano, M. Fukata (Nagoya University), H. Qadota and N. Inagaki (Nara Institute of Science and Technology) for their helpful discussions, T. Kimura, T. Shiromizu, H. Watanabe and M. Yoshizaki for preparing some materials and technical assistance, and T. Ishii for secretarial assistance. This research was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan and the organization for Pharmaceutical Safety and Research.",

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AU - Nishimura, Takashi

AU - Fukata, Yuko

AU - Kato, Katsuhiro

AU - Yamaguchi, Tomoya

AU - Matsuura, Yoshiharu

AU - Kamiguchi, Hiroyuki

AU - Kaibuchi, Kozo

N1 - Funding Information: We thank Y. Gu, Y. Ihara, A. Craig, M. Nakafuku, A. Tokunaga, H. Okano and V. Lemmon for their kind gifts of materials. We also thank M. Amano, M. Fukata (Nagoya University), H. Qadota and N. Inagaki (Nara Institute of Science and Technology) for their helpful discussions, T. Kimura, T. Shiromizu, H. Watanabe and M. Yoshizaki for preparing some materials and technical assistance, and T. Ishii for secretarial assistance. This research was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan and the organization for Pharmaceutical Safety and Research.

PY - 2003/9/1

Y1 - 2003/9/1

N2 - Axon growth during neural development is highly dependent on both cytoskeletal re-organization and polarized membrane trafficking. Previously, we demonstrated that collapsin response mediator protein-2 (CRMP-2) is critical for specifying axon/dendrite fate and axon growth in cultured hippocampal neurons, possibly by interacting with tubulin heterodimers and promoting microtubule assembly. Here, we identify Numb as a CRMP-2-interacting protein. Numb has been shown to interact with α-adaptin and to be involved in endocytosis. We found that Numb was associated with L1, a neuronal cell adhesion molecule that is endocytosed and recycled at the growth cone, where CRMP-2 and Numb were colocalized. Furthermore, expression of dominant-negative CRMP-2 mutants or knockdown of CRMP-2 message with small-interfering (si) RNA inhibited endocytosis of L1 at axonal growth cones and suppressed axon growth. These results suggest that in addition to regulating microtubule assembly, CRMP-2 is involved in polarized Numb-mediated endocytosis of proteins such as L1.

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CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth

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