TY - JOUR
T1 - GSK-3β regulates phosphorylation of CRMP-2 and neuronal polarity
AU - Yoshimura, Takeshi
AU - Kawano, Yoji
AU - Arimura, Nariko
AU - Kawabata, Saeko
AU - Kikuchi, Akira
AU - Kaibuchi, Kozo
N1 - Funding Information:
We thank Drs. Y. Ihara (University of Tokyo, Tokyo, Japan) and David L. Turner (University of Michigan, MI) for their kind gifts of materials; Drs. Y. Rao (Washington University, MO), Y. Goshima (Yokohama City University, Kanagawa, Japan), M. Amano, M. Fukata, Y. Fukata, S. Taya, C. Menager, T. Nishimura, Miss K. Fujii, and Mr. A. Hattori for helpful discussion; Miss K. Yamada for preparing some materials and technical assistance; and Mrs. T. Ishii for secretarial assistance. This research was supported in part by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); grant-in-aid for Creative Scientific Research from MEXT; The 21st Century Centre of Excellence (COE) Program from MEXT; special coordination funds for promoting Science and Technology (SCFPST); and the Pharmaceuticals and Medical Devices Agency (PMDA).
PY - 2005/1/14
Y1 - 2005/1/14
N2 - Neurons are highly polarized and comprised of two structurally and functionally distinct parts, an axon and dendrites. We previously showed that collapsin response mediator protein-2 (CRMP-2) is critical for specifying axon/dendrite fate, possibly by promoting neurite elongation via microtubule assembly. Here, we showed that glycogen synthase kinase-3β (GSK-3β) phosphorylated CRMP-2 at Thr-514 and inactivated it. The expression of the nonphosphorylated form of CRMP-2 or inhibition of GSK-3β induced the formation of multiple axon-like neurites in hippocampal neurons. The expression of constitutively active GSK-3β impaired neuronal polarization, whereas the nonphosphorylated form of CRMP-2 counteracted the inhibitory effects of GSK-3β, indicating that GSK-3β regulates neuronal polarity through the phosphorylation of CRMP-2. Treatment of hippocampal neurons with neurotrophin-3 (NT-3) induced inactivation of GSK-3β and dephosphorylation of CRMP-2. Knockdown of CRMP-2 inhibited NT-3-induced axon outgrowth. These results suggest that NT-3 decreases phosphorylated CRMP-2 and increases nonphosphorylated active CRMP-2, thereby promoting axon outgrowth.
AB - Neurons are highly polarized and comprised of two structurally and functionally distinct parts, an axon and dendrites. We previously showed that collapsin response mediator protein-2 (CRMP-2) is critical for specifying axon/dendrite fate, possibly by promoting neurite elongation via microtubule assembly. Here, we showed that glycogen synthase kinase-3β (GSK-3β) phosphorylated CRMP-2 at Thr-514 and inactivated it. The expression of the nonphosphorylated form of CRMP-2 or inhibition of GSK-3β induced the formation of multiple axon-like neurites in hippocampal neurons. The expression of constitutively active GSK-3β impaired neuronal polarization, whereas the nonphosphorylated form of CRMP-2 counteracted the inhibitory effects of GSK-3β, indicating that GSK-3β regulates neuronal polarity through the phosphorylation of CRMP-2. Treatment of hippocampal neurons with neurotrophin-3 (NT-3) induced inactivation of GSK-3β and dephosphorylation of CRMP-2. Knockdown of CRMP-2 inhibited NT-3-induced axon outgrowth. These results suggest that NT-3 decreases phosphorylated CRMP-2 and increases nonphosphorylated active CRMP-2, thereby promoting axon outgrowth.
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U2 - 10.1016/j.cell.2004.11.012
DO - 10.1016/j.cell.2004.11.012
M3 - Article
C2 - 15652488
AN - SCOPUS:11844297771
SN - 0092-8674
VL - 120
SP - 137
EP - 149
JO - Cell
JF - Cell
IS - 1
ER -