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 journalArticlepeer-review

209 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 languageEnglish
Pages (from-to)819-826
Number of pages8
JournalNature Cell Biology
Volume5
Issue number9
DOIs
Publication statusPublished - 01-09-2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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