An inactive pool of GSK-3 at the leading edge of growth cones is implicated in Semaphorin 3A signaling

doi:10.1083/jcb.200201098

PeproTech: Your source for Cell Biology Research Reagents

Published 15 April 2002. doi:10.1083/jcb.200201098

This Article

	Full Text
	PDF (Full Text)
	PPT slides of all figures
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Eickholt, B. J.
	Articles by Doherty, P.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Eickholt, B. J.
	Articles by Doherty, P.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0021-9525/2002/4/211 $5.00
The Journal of Cell Biology, Volume 157, Number 2, April 15, 2002 211-217

Report

An inactive pool of GSK-3 at the leading edge of growth cones is implicated in Semaphorin 3A signaling

Britta J. Eickholt¹, Frank S. Walsh² and Patrick Doherty¹

¹ Molecular Neurobiology Group, Medical Research Council Centre for Developmental Biology, King's College London, London SE1 1UL, United Kingdom
² Neurology Centre of Excellence in Drug Discovery, GlaxoSmithKline Pharmaceuticals, Harlow, Essex CM19 5AW, United Kingdom

Address correspondence to Britta J. Eickholt, Molecular Neurobiology Group, MRC Centre for Developmental Biology, King's College London, London SE1 1UL, UK. Tel.: 44-20-7848-6812. Fax: 44-20-7848-6816. E-mail: Britta.J.Eickholt{at}kcl.ac.uk

Glycogen synthase kinase (GSK)-3 is a serine/threonine kinasethat has been implicated in several aspects in embryonic developmentand several growth factor signaling cascades. We now reportthat an inactive phosphorylated pool of the enzyme colocalizeswith F-actin in both neuronal and nonneuronal cells. Semaphorin3A (Sema 3A), a molecule that inhibits axonal growth, activatesGSK-3 at the leading edge of neuronal growth cones and in Sema3A–responsive human breast cancer cells, suggesting thatGSK-3 activity might play a role in coupling Sema 3A signalingto changes in cell motility. We show that three different GSK-3antagonists (LiCl, SB-216763, and SB-415286) can inhibit thegrowth cone collapse response induced by Sema 3A. These studiesreveal a novel compartmentalization of inactive GSK-3 in cellsand demonstrate for the first time a requirement for GSK-3 activityin the Sema 3A signal transduction pathway.

Key Words: GSK-3; axon guidance; actin; Semaphorin 3A; growth cone

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Dill, J., Wang, H., Zhou, F., Li, S. (2008). Inactivation of Glycogen Synthase Kinase 3 Promotes Axonal Growth and Recovery in the CNS. J. Neurosci. 28: 8914-8928 [Abstract] [Full Text]
Eickholt, B. J. (2008). Functional diversity and mechanisms of action of the semaphorins. Development 135: 2689-2694 [Abstract] [Full Text]
Timm, T., Balusamy, K., Li, X., Biernat, J., Mandelkow, E., Mandelkow, E.-M. (2008). Glycogen Synthase Kinase (GSK) 3{beta} Directly Phosphorylates Serine 212 in the Regulatory Loop and Inhibits Microtubule Affinity-regulating Kinase (MARK) 2. J. Biol. Chem. 283: 18873-18882 [Abstract] [Full Text]
Cosker, K. E., Shadan, S., van Diepen, M., Morgan, C., Li, M., Allen-Baume, V., Hobbs, C., Doherty, P., Cockcroft, S., Eickholt, B. J. (2008). Regulation of PI3K signalling by the phosphatidylinositol transfer protein PITP{alpha} during axonal extension in hippocampal neurons. J. Cell Sci. 121: 796-803 [Abstract] [Full Text]
Schmidt, E. F., Shim, S.-O., Strittmatter, S. M. (2008). Release of MICAL Autoinhibition by Semaphorin-Plexin Signaling Promotes Interaction with Collapsin Response Mediator Protein. J. Neurosci. 28: 2287-2297 [Abstract] [Full Text]
Chen, P., Gu, Z., Liu, W., Yan, Z. (2007). Glycogen Synthase Kinase 3 Regulates N-Methyl-D-aspartate Receptor Channel Trafficking and Function in Cortical Neurons. Mol. Pharmacol. 72: 40-51 [Abstract] [Full Text]
Shimshoni, J. A., Dalton, E. C., Jenkins, A., Eyal, S., Ewan, K., Williams, R. S. B., Pessah, N., Yagen, B., Harwood, A. J., Bialer, M. (2007). The Effects of Central Nervous System-Active Valproic Acid Constitutional Isomers, Cyclopropyl Analogs, and Amide Derivatives on Neuronal Growth Cone Behavior. Mol. Pharmacol. 71: 884-892 [Abstract] [Full Text]
Gartner, A., Huang, X., Hall, A. (2006). Neuronal polarity is regulated by glycogen synthase kinase-3 (GSK-3{beta}) independently of Akt/PKB serine phosphorylation. J. Cell Sci. 119: 3927-3934 [Abstract] [Full Text]
Cole, A. R., Causeret, F., Yadirgi, G., Hastie, C. J., McLauchlan, H., McManus, E. J., Hernandez, F., Eickholt, B. J., Nikolic, M., Sutherland, C. (2006). Distinct Priming Kinases Contribute to Differential Regulation of Collapsin Response Mediator Proteins by Glycogen Synthase Kinase-3 in Vivo. J. Biol. Chem. 281: 16591-16598 [Abstract] [Full Text]
Togashi, H., Schmidt, E. F., Strittmatter, S. M. (2006). RanBPM contributes to Semaphorin3A signaling through plexin-A receptors.. J. Neurosci. 26: 4961-4969 [Abstract] [Full Text]
Sayas, C. L., Ariaens, A., Ponsioen, B., Moolenaar, W. H. (2006). GSK-3 Is Activated by the Tyrosine Kinase Pyk2 during LPA1-mediated Neurite Retraction. Mol. Biol. Cell 17: 1834-1844 [Abstract] [Full Text]
Chadborn, N. H., Ahmed, A. I., Holt, M. R., Prinjha, R., Dunn, G. A., Jones, G. E., Eickholt, B. J. (2006). PTEN couples Sema3A signalling to growth cone collapse.. J. Cell Sci. 119: 951-957 [Abstract] [Full Text]
Kobayashi, T., Hino, S.-i., Oue, N., Asahara, T., Zollo, M., Yasui, W., Kikuchi, A. (2006). Glycogen Synthase Kinase 3 and h-prune Regulate Cell Migration by Modulating Focal Adhesions. Mol. Cell. Biol. 26: 898-911 [Abstract] [Full Text]
Votin, V., Nelson, W. J., Barth, A. I. M. (2005). Neurite outgrowth involves adenomatous polyposis coli protein and {beta}-catenin. J. Cell Sci. 118: 5699-5708 [Abstract] [Full Text]
Arimura, N., Menager, C., Kawano, Y., Yoshimura, T., Kawabata, S., Hattori, A., Fukata, Y., Amano, M., Goshima, Y., Inagaki, M., Morone, N., Usukura, J., Kaibuchi, K. (2005). Phosphorylation by Rho Kinase Regulates CRMP-2 Activity in Growth Cones. Mol. Cell. Biol. 25: 9973-9984 [Abstract] [Full Text]
Bazzoni, G., Tonetti, P., Manzi, L., Cera, M. R., Balconi, G., Dejana, E. (2005). Expression of junctional adhesion molecule-A prevents spontaneous and random motility. J. Cell Sci. 118: 623-632 [Abstract] [Full Text]
Uchida, Y., Ohshima, T., Sasaki, Y., Suzuki, H., Yanai, S., Yamashita, N., Nakamura, F., Takei, K., Ihara, Y., Mikoshiba, K., Kolattukudy, P., Honnorat, J., Goshima, Y. (2005). Semaphorin3A signalling is mediated via sequential Cdk5 and GSK3{beta} phosphorylation of CRMP2: implication of common phosphorylating mechanism underlying axon guidance and Alzheimer's disease. GENES CELLS 10: 165-179 [Abstract] [Full Text]
Brown, M., Jacobs, T., Eickholt, B., Ferrari, G., Teo, M., Monfries, C., Qi, R. Z., Leung, T., Lim, L., Hall, C. (2004). {alpha}2-Chimaerin, Cyclin-Dependent Kinase 5/p35, and Its Target Collapsin Response Mediator Protein-2 Are Essential Components in Semaphorin 3A-Induced Growth-Cone Collapse. J. Neurosci. 24: 8994-9004 [Abstract] [Full Text]
O'Brien, W. T., Harper, A. D., Jove, F., Woodgett, J. R., Maretto, S., Piccolo, S., Klein, P. S. (2004). Glycogen Synthase Kinase-3{beta} Haploinsufficiency Mimics the Behavioral and Molecular Effects of Lithium. J. Neurosci. 24: 6791-6798 [Abstract] [Full Text]
Caricasole, A., Ferraro, T., Iacovelli, L., Barletta, E., Caruso, A., Melchiorri, D., Terstappen, G. C., Nicoletti, F. (2003). Functional Characterization of WNT7A Signaling in PC12 Cells: INTERACTION WITH A FZD5{middle dot}LRP6 RECEPTOR COMPLEX AND MODULATION BY DICKKOPF PROTEINS. J. Biol. Chem. 278: 37024-37031 [Abstract] [Full Text]
Atwal, J. K., Singh, K. K., Tessier-Lavigne, M., Miller, F. D., Kaplan, D. R. (2003). Semaphorin 3F Antagonizes Neurotrophin-Induced Phosphatidylinositol 3-Kinase and Mitogen-Activated Protein Kinase Kinase Signaling: A Mechanism for Growth Cone Collapse. J. Neurosci. 23: 7602-7609 [Abstract] [Full Text]
Beffert, U., Morfini, G., Bock, H. H., Reyna, H., Brady, S. T., Herz, J. (2002). Reelin-mediated Signaling Locally Regulates Protein Kinase B/Akt and Glycogen Synthase Kinase 3beta. J. Biol. Chem. 277: 49958-49964 [Abstract] [Full Text]
Tokuoka, H., Yoshida, T., Matsuda, N., Mishina, M. (2002). Regulation by Glycogen Synthase Kinase-3beta of the Arborization Field and Maturation of Retinotectal Projection in Zebrafish. J. Neurosci. 22: 10324-10332 [Abstract] [Full Text]
Wang, Q., Wang, X., Hernandez, A., Hellmich, M. R., Gatalica, Z., Evers, B. M. (2002). Regulation of TRAIL Expression by the Phosphatidylinositol 3-Kinase/Akt/GSK-3 Pathway in Human Colon Cancer Cells. J. Biol. Chem. 277: 36602-36610 [Abstract] [Full Text]