CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth
Author: ["Takashi Nishimura","Yuko Fukata","Katsuhiro Kato","Tomoya Yamaguchi","Yoshiharu Matsuura","Hiroyuki Kamiguchi","Kozo Kaibuchi"]
Publication: Nature Cell Biology
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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.
Cite this article
Nishimura, T., Fukata, Y., Kato, K. et al. CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth. Nat Cell Biol 5, 819–826 (2003). https://doi.org/10.1038/ncb1039
