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.
Mesh Terms:
Animals, Cell Differentiation, Cell Polarity, Cells, Cultured, Central Nervous System, Endocytosis, Fetus, Growth Cones, Hippocampus, Intercellular Signaling Peptides and Proteins, Membrane Proteins, Microtubules, Mutation, Nerve Tissue Proteins, Neural Cell Adhesion Molecule L1, Protein Transport, RNA Interference, Rats
Animals, Cell Differentiation, Cell Polarity, Cells, Cultured, Central Nervous System, Endocytosis, Fetus, Growth Cones, Hippocampus, Intercellular Signaling Peptides and Proteins, Membrane Proteins, Microtubules, Mutation, Nerve Tissue Proteins, Neural Cell Adhesion Molecule L1, Protein Transport, RNA Interference, Rats
Nat. Cell Biol.
Date: Sep. 01, 2003
PubMed ID: 12942088
View in: Pubmed Google Scholar
Download Curated Data For This Publication
8803
Switch View:
- Interactions 11