HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 48, 50176-50180, November 26, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/48/50176    most recent C400412200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cole, A. R. Articles by Sutherland, C. Search for Related Content PubMed PubMed Citation Articles by Cole, A. R. Articles by Sutherland, C. Social Bookmarking                      What's this?

GSK-3 Phosphorylation of the Alzheimer Epitope within Collapsin Response Mediator Proteins Regulates Axon Elongation in Primary Neurons^*

Adam R. Cole, Axel Knebel, Nick A. Morrice¶, Laura A. Robertson, Andrew J. Irving, Chris N. Connolly, and Calum Sutherland, Recipient of the Diabetes UK Senior Fellowship (02/0002473)||

From the Division of Pathology and Neurosciences, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, Scotland, Kinasource, Laboratory 4.21, MSI/WTB Building, School of Life Sciences, University of Dundee, Dundee DD1 4HN, Scotland, and the ^¶Medical Research Council Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 4HN, Scotland

Elevated glycogen synthase kinase-3 (GSK-3) activity is associated with Alzheimer disease. We have found that collapsin response mediator proteins (CRMP) 2 and 4 are physiological substrates of GSK-3. The amino acids targeted by GSK-3 comprise a hyperphosphorylated epitope first identified in plaques isolated from Alzheimer brain. Expression of wild type CRMP2 in primary hippocampal neurons or SH-SY5Y neuroblastoma cells promotes axon elongation. However, a GSK-3-insensitive CRMP2 mutant has dramatically reduced ability to promote axon elongation, a similar effect to pharmacological inhibition of GSK-3. Hence, we propose that phosphorylation of CRMP proteins by GSK-3 regulates axon elongation. This work provides a direct connection between hyperphosphorylation of these residues and elevated GSK-3 activity, both of which are observed in Alzheimer brain.

Received for publication, September 3, 2004

^* This work was supported in part by the Biotechnology and Biological Sciences Research Council (94/C18727). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed. Tel.: 44-1382-632507; E-mail: c.d.sutherland{at}dundee.ac.uk.

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

This article has been cited by other articles:

				M. O. Collins, L. Yu, I. Campuzano, S. G. N. Grant, and J. S. Choudhary Phosphoproteomic Analysis of the Mouse Brain Cytosol Reveals a Predominance of Protein Phosphorylation in Regions of Intrinsic Sequence Disorder Mol. Cell. Proteomics, July 1, 2008; 7(7): 1331 - 1348. [Abstract] [Full Text] [PDF]

				A. R. Cole, M. P. M. Soutar, M. Rembutsu, L. van Aalten, C. J. Hastie, H. Mclauchlan, M. Peggie, M. Balastik, K. P. Lu, and C. Sutherland Relative Resistance of Cdk5-phosphorylated CRMP2 to Dephosphorylation J. Biol. Chem., June 27, 2008; 283(26): 18227 - 18237. [Abstract] [Full Text] [PDF]

				V. Rogemond, C. Auger, P. Giraudon, M. Becchi, N. Auvergnon, M.-F. Belin, J. Honnorat, and M. Moradi-Ameli Processing and Nuclear Localization of CRMP2 during Brain Development Induce Neurite Outgrowth Inhibition J. Biol. Chem., May 23, 2008; 283(21): 14751 - 14761. [Abstract] [Full Text] [PDF]

				S. Petratos, Q.-X. Li, A. J. George, X. Hou, M. L. Kerr, S. E. Unabia, I. Hatzinisiriou, D. Maksel, M.-I. Aguilar, and D. H. Small The -amyloid protein of Alzheimer's disease increases neuronal CRMP-2 phosphorylation by a Rho-GTP mechanism Brain, January 1, 2008; 131(1): 90 - 108. [Abstract] [Full Text] [PDF]

				B. P. S. Vohra, M. Fu, and R. O. Heuckeroth Protein Kinase C{zeta} and Glycogen Synthase Kinase-3{beta} Control Neuronal Polarity in Developing Rodent Enteric Neurons, whereas SMAD Specific E3 Ubiquitin Protein Ligase 1 Promotes Neurite Growth But Does Not Influence Polarity J. Neurosci., August 29, 2007; 27(35): 9458 - 9468. [Abstract] [Full Text] [PDF]

				R. A. Rissman, K.-F. Lee, W. Vale, and P. E. Sawchenko Corticotropin-Releasing Factor Receptors Differentially Regulate Stress-Induced Tau Phosphorylation J. Neurosci., June 13, 2007; 27(24): 6552 - 6562. [Abstract] [Full Text] [PDF]

				L. G. Puente, S. Voisin, R. E. C. Lee, and L. A. Megeney Reconstructing the Regulatory Kinase Pathways of Myogenesis from Phosphopeptide Data Mol. Cell. Proteomics, December 1, 2006; 5(12): 2244 - 2251. [Abstract] [Full Text] [PDF]

				Y. Horiuchi, A. Asada, S.-i. Hisanaga, A. Toh-e, and M. Nishizawa Identifying novel substrates for mouse Cdk5 kinase using the yeast Saccharomyces cerevisiae Genes Cells, December 1, 2006; 11(12): 1393 - 1404. [Abstract] [Full Text] [PDF]

				A. R. Cole, F. Causeret, G. Yadirgi, C. J. Hastie, H. McLauchlan, E. J. McManus, F. Hernandez, B. J. Eickholt, M. Nikolic, and C. Sutherland Distinct Priming Kinases Contribute to Differential Regulation of Collapsin Response Mediator Proteins by Glycogen Synthase Kinase-3 in Vivo J. Biol. Chem., June 16, 2006; 281(24): 16591 - 16598. [Abstract] [Full Text] [PDF]

				H. Steen, J. A. Jebanathirajah, J. Rush, N. Morrice, and M. W. Kirschner Phosphorylation Analysis by Mass Spectrometry: Myths, Facts, and the Consequences for Qualitative and Quantitative Measurements Mol. Cell. Proteomics, January 1, 2006; 5(1): 172 - 181. [Abstract] [Full Text] [PDF]

				N. Arimura, C. Menager, Y. Kawano, T. Yoshimura, S. Kawabata, A. Hattori, Y. Fukata, M. Amano, Y. Goshima, M. Inagaki, et al. Phosphorylation by Rho Kinase Regulates CRMP-2 Activity in Growth Cones Mol. Cell. Biol., November 15, 2005; 25(22): 9973 - 9984. [Abstract] [Full Text] [PDF]

				M. E. Cuomo, A. Knebel, G. Platt, N. Morrice, P. Cohen, and S. Mittnacht Regulation of Microfilament Organization by Kaposi Sarcoma-associated Herpes Virus-cyclin{middle dot}CDK6 Phosphorylation of Caldesmon J. Biol. Chem., October 28, 2005; 280(43): 35844 - 35858. [Abstract] [Full Text] [PDF]

				K. A. Ryan and S. W. Pimplikar Activation of GSK-3 and phosphorylation of CRMP2 in transgenic mice expressing APP intracellular domain J. Cell Biol., October 24, 2005; 171(2): 327 - 335. [Abstract] [Full Text] [PDF]

				M. R. Larsen, T. E. Thingholm, O. N. Jensen, P. Roepstorff, and T. J. D. Jorgensen Highly Selective Enrichment of Phosphorylated Peptides from Peptide Mixtures Using Titanium Dioxide Microcolumns Mol. Cell. Proteomics, July 1, 2005; 4(7): 873 - 886. [Abstract] [Full Text] [PDF]

				N. Trivedi, P. Marsh, R. G. Goold, A. Wood-Kaczmar, and P. R. Gordon-Weeks Glycogen synthase kinase-3{beta} phosphorylation of MAP1B at Ser1260 and Thr1265 is spatially restricted to growing axons J. Cell Sci., March 1, 2005; 118(5): 993 - 1005. [Abstract] [Full Text] [PDF]

				Y. Uchida, T. Ohshima, Y. Sasaki, H. Suzuki, S. Yanai, N. Yamashita, F. Nakamura, K. Takei, Y. Ihara, K. Mikoshiba, et al. 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, February 1, 2005; 10(2): 165 - 179. [Abstract] [Full Text] [PDF]