Nature Cell Biology
5, 819 - 826 (2003)
Published online: 24 August 2003; | doi:10.1038/ncb1039
CRMP-2 regulates polarized Numb-mediated endocytosis for axon growthTakashi Nishimura1, Yuko Fukata1, Katsuhiro Kato1, Tomoya Yamaguchi1, Yoshiharu Matsuura2, Hiroyuki Kamiguchi3
& Kozo Kaibuchi11
Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa, Nagoya, Aichi 466-8550, Japan. 2
Research Center for Emerging Infectious Disease, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. 3
Developmental Brain Science Group, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Correspondence should be addressed to Kozo Kaibuchi kaibuchi@med.nagoya-u.ac.jpAxon 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  -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.
|
