CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth.
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 alpha-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.
Nishimura
Takashi
T
Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa, Nagoya, Aichi 466-8550, Japan.
Fukata
Yuko
Y
Kato
Katsuhiro
K
Yamaguchi
Tomoya
T
Matsuura
Yoshiharu
Y
Kamiguchi
Hiroyuki
H
Kaibuchi
Kozo
K
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D016764:Cell Polarity / Q000235:genetics; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D005333:Fetus; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology*; D034622:RNA Interference / Q000502:physiology; D051381:Rats
D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; C106293:Numb protein, mouse; C095114:collapsin response mediator protein-2