|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
Journal of Cell Science, Vol 112, Issue 19 3373-3384, Copyright © 1999 by Company of Biologists
JOURNAL ARTICLES |
RG Goold, R Owen and PR Gordon-Weeks
Developmental Biology Research Centre, The Randall Institute, King's College London, London WC2B 5RL, UK.
We have recently shown that glycogen synthase kinase 3beta (GSK3beta) phosphorylates the microtubule-associated protein (MAP) 1B in an in vitro kinase assay and in cultured cerebellar granule cells. Mapping studies identified a region of MAP1B high in serine-proline motifs that is phosphorylated by GSK3beta. Here we show that COS cells, transiently transfected with both MAP1B and GSK3beta, express high levels of the phosphorylated isoform of MAP1B (MAP1B-P) generated by GSK3beta. To investigate effects of MAP1B-P on microtubule dynamics, double transfected cells were labelled with antibodies to tyrosinated and detyrosinated tubulin markers for stable and unstable microtubules. This showed that high levels of MAP1B-P expression are associated with the loss of a population of detyrosinated microtubules in these cells. Transfection with MAP1B protected microtubules in COS cells against nocodazole depolymerisation, confirming previous studies. However, this protective effect was greatly reduced in cells containing high levels of MAP1B-P following transfection with both MAP1B and GSK3beta. Since we also found that MAP1B binds to tyrosinated, but not to detyrosinated, microtubules in transfected cells, we propose that MAP1B-P prevents tubulin detyrosination and subsequent conversion of unstable to stable microtubules and that this involves binding of MAP1B-P to unstable microtubules. The highest levels of MAP1B-P are found in neuronal growth cones and therefore our findings suggest that a primary role of MAP1B-P in growing axons may be to maintain growth cone microtubules in a dynamically unstable state, a known requirement of growth cone microtubules during pathfinding. To test this prediction, we reduced the levels of MAP1B-P in neuronal growth cones of dorsal root ganglion cells in culture by inhibiting GSK3beta with lithium. In confirmation of the proposed role of MAP1B-P in maintaining microtubule dynamics we found that lithium treatment dramatically increased the numbers of stable (detyrosinated) microtubules in the growth cones of these neurons.
This article has been cited by other articles:
![]() |
T. M. E. Scales, S. Lin, M. Kraus, R. G. Goold, and P. R. Gordon-Weeks Nonprimed and DYRK1A-primed GSK3{beta}-phosphorylation sites on MAP1B regulate microtubule dynamics in growing axons J. Cell Sci., July 15, 2009; 122(14): 2424 - 2435. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Miech, H.-U. Pauer, X. He, and T. L. Schwarz Presynaptic Local Signaling by a Canonical Wingless Pathway Regulates Development of the Drosophila Neuromuscular Junction J. Neurosci., October 22, 2008; 28(43): 10875 - 10884. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. A. Purro, L. Ciani, M. Hoyos-Flight, E. Stamatakou, E. Siomou, and P. C. Salinas Wnt Regulates Axon Behavior through Changes in Microtubule Growth Directionality: A New Role for Adenomatous Polyposis Coli J. Neurosci., August 20, 2008; 28(34): 8644 - 8654. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Witte, D. Neukirchen, and F. Bradke Microtubule stabilization specifies initial neuronal polarization J. Cell Biol., February 6, 2008; 180(3): 619 - 632. [Abstract] [Full Text] [PDF] |
||||
![]() |
T.-S. Cheng, Y.-L. Hsiao, C.-C. Lin, C.-T. R. Yu, C.-M. Hsu, M.-S. Chang, C.-I Lee, C.-Y. F. Huang, S.-L. Howng, and Y.-R. Hong Glycogen Synthase Kinase 3 Interacts with and Phosphorylates the Spindle-associated Protein Astrin J. Biol. Chem., January 25, 2008; 283(4): 2454 - 2464. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. O. Nowicki, N. Dmitrieva, A. M. Stein, J. L. Cutter, J. Godlewski, Y. Saeki, M. Nita, M. E. Berens, L. M. Sander, H. B. Newton, et al. Lithium inhibits invasion of glioma cells; possible involvement of glycogen synthase kinase-3 Neuro-oncol, January 1, 2008; 10(5): 690 - 699. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. H. Eng, T. M. Huckaba, and G. G. Gundersen The Formin mDia Regulates GSK3beta through Novel PKCs to Promote Microtubule Stabilization but Not MTOC Reorientation in Migrating Fibroblasts Mol. Biol. Cell, December 1, 2006; 17(12): 5004 - 5016. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. C. Yang, C. H. Lin, and E. H. Y. Lee Serum- and Glucocorticoid-Inducible Kinase 1 (SGK1) Increases Neurite Formation through Microtubule Depolymerization by SGK1 and by SGK1 Phosphorylation of tau Mol. Cell. Biol., November 15, 2006; 26(22): 8357 - 8370. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Seng, H. K. Avraham, S. Jiang, S. Venkatesh, and S. Avraham KLHL1/MRP2 Mediates Neurite Outgrowth in a Glycogen Synthase Kinase 3{beta}-Dependent Manner Mol. Cell. Biol., November 15, 2006; 26(22): 8371 - 8384. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Yoshimura, N. Arimura, and K. Kaibuchi Signaling networks in neuronal polarization. J. Neurosci., October 18, 2006; 26(42): 10626 - 10630. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Pellinen and J. Ivaska Integrin traffic. J. Cell Sci., September 15, 2006; 119(Pt 18): 3723 - 3731. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. M. Viquez, C. R. Li, Y. P. Wairkar, and A. DiAntonio The B' Protein Phosphatase 2A Regulatory Subunit well-rounded Regulates Synaptic Growth and Cytoskeletal Stability at the Drosophila Neuromuscular Junction J. Neurosci., September 6, 2006; 26(36): 9293 - 9303. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Hergovich, J. Lisztwan, C. R. Thoma, C. Wirbelauer, R. E. Barry, and W. Krek Priming-Dependent Phosphorylation and Regulation of the Tumor Suppressor pVHL by Glycogen Synthase Kinase 3 Mol. Cell. Biol., August 1, 2006; 26(15): 5784 - 5796. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. M. Chen, Q. J. Wang, H. S. Hu, P. C. Yu, J. Zhu, G. Drewes, H. Piwnica-Worms, and Z. G. Luo Microtubule affinity-regulating kinase 2 functions downstream of the PAR-3/PAR-6/atypical PKC complex in regulating hippocampal neuronal polarity PNAS, May 30, 2006; 103(22): 8534 - 8539. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Cai, M. Li, J. Vrana, and M. D. Schaller Glycogen synthase kinase 3- and extracellular signal-regulated kinase-dependent phosphorylation of paxillin regulates cytoskeletal rearrangement. Mol. Cell. Biol., April 1, 2006; 26(7): 2857 - 2868. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. M. Ooms, C. G. Fedele, M. V. Astle, I. Ivetac, V. Cheung, R. B. Pearson, M. J. Layton, A. Forrai, H. H. Nandurkar, and C. A. Mitchell The Inositol Polyphosphate 5-Phosphatase, PIPP, Is a Novel Regulator of Phosphoinositide 3-Kinase-dependent Neurite Elongation Mol. Biol. Cell, February 1, 2006; 17(2): 607 - 622. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Gonzalez-Billault, J. A. Del Rio, J. M. Urena, E. M. Jimenez-Mateos, M. J. Barallobre, M. Pascual, L. Pujadas, S. Simo, A. L. Torre, R. Gavin, et al. A role of MAP1B in Reelin-dependent Neuronal Migration Cereb Cortex, August 1, 2005; 15(8): 1134 - 1145. [Abstract] [Full Text] [PDF] |
||||
![]() |
S.-O. Yoon, S. Shin, and A. M. Mercurio Hypoxia Stimulates Carcinoma Invasion by Stabilizing Microtubules and Promoting the Rab11 Trafficking of the {alpha}6{beta}4 Integrin Cancer Res., April 1, 2005; 65(7): 2761 - 2769. [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] |
||||
![]() |
G. Bazzoni, P. Tonetti, L. Manzi, M. R. Cera, G. Balconi, and E. Dejana Expression of junctional adhesion molecule-A prevents spontaneous and random motility J. Cell Sci., February 1, 2005; 118(3): 623 - 632. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Lu, H. Wang, Z. Liang, L. Ku, W. T. O'Donnell, W. Li, S. T. Warren, and Y. Feng The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development PNAS, October 19, 2004; 101(42): 15201 - 15206. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Bouquet, S. Soares, Y. von Boxberg, M. Ravaille-Veron, F. Propst, and F. Nothias Microtubule-Associated Protein 1B Controls Directionality of Growth Cone Migration and Axonal Branching in Regeneration of Adult Dorsal Root Ganglia Neurons J. Neurosci., August 11, 2004; 24(32): 7204 - 7213. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. T. O'Brien, A. D. Harper, F. Jove, J. R. Woodgett, S. Maretto, S. Piccolo, and P. S. Klein Glycogen Synthase Kinase-3{beta} Haploinsufficiency Mimics the Behavioral and Molecular Effects of Lithium J. Neurosci., July 28, 2004; 24(30): 6791 - 6798. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Ciani, O. Krylova, M. J. Smalley, T. C. Dale, and P. C. Salinas A divergent canonical WNT-signaling pathway regulates microtubule dynamics: Dishevelled signals locally to stabilize microtubules J. Cell Biol., January 19, 2004; 164(2): 243 - 253. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. W. Grabham, B. Reznik, and D. J. Goldberg Microtubule and Rac 1-dependent F-actin in growth cones J. Cell Sci., September 15, 2003; 116(18): 3739 - 3748. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Opal, J. J. Garcia, F. Propst, A. Matilla, H. T. Orr, and H. Y. Zoghbi Mapmodulin/Leucine-rich Acidic Nuclear Protein Binds the Light Chain of Microtubule-associated Protein 1B and Modulates Neuritogenesis J. Biol. Chem., September 5, 2003; 278(36): 34691 - 34699. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Bomont and M. Koenig Intermediate filament aggregation in fibroblasts of giant axonal neuropathy patients is aggravated in non dividing cells and by microtubule destabilization Hum. Mol. Genet., April 15, 2003; 12(8): 813 - 822. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. G. Wakefield, D. J. Stephens, and J. M. Tavare A role for glycogen synthase kinase-3 in mitotic spindle dynamics and chromosome alignment J. Cell Sci., February 15, 2003; 116(4): 637 - 646. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. L. Sayas, J. Avila, and F. Wandosell Glycogen Synthase Kinase-3 Is Activated in Neuronal Cells by Galpha 12 and Galpha 13 by Rho-Independent and Rho-Dependent Mechanisms J. Neurosci., August 15, 2002; 22(16): 6863 - 6875. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. J. Eickholt, F. S. Walsh, and P. Doherty An inactive pool of GSK-3 at the leading edge of growth cones is implicated in Semaphorin 3A signaling J. Cell Biol., April 15, 2002; 157(2): 211 - 217. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Gonzalez-Billault, J. Avila, and A. Caceres Evidence for the Role of MAP1B in Axon Formation Mol. Biol. Cell, July 1, 2001; 12(7): 2087 - 2098. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Kabir, A. W. Schaefer, A. Nakhost, W. S. Sossin, and P. Forscher Protein Kinase C Activation Promotes Microtubule Advance in Neuronal Growth Cones by Increasing Average Microtubule Growth Lifetimes J. Cell Biol., March 5, 2001; 152(5): 1033 - 1044. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. G. Goold and P. R. Gordon-Weeks Microtubule-associated protein 1B phosphorylation by glycogen synthase kinase 3{beta} is induced during PC12 cell differentiation J. Cell Sci., January 12, 2001; 114(23): 4273 - 4284. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. Krylova, M. J. Messenger, and P. C. Salinas Dishevelled-1 Regulates Microtubule Stability: A New Function Mediated by Glycogen Synthase Kinase-3{beta} J. Cell Biol., October 3, 2000; 151(1): 83 - 94. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Pattnaik, A. Jellali, J. Sahel, H. Dreyfus, and S. Picaud GABAC Receptors Are Localized with Microtubule-Associated Protein 1B in Mammalian Cone Photoreceptors J. Neurosci., September 15, 2000; 20(18): 6789 - 6796. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. B. Rosso, A. O. Caceres, A. M. E. de Duffard, R. O. Duffard, and S. Quiroga 2,4-Dichlorophenoxyacetic Acid Disrupts the Cytoskeleton and Disorganizes the Golgi Apparatus of Cultured Neurons Toxicol. Sci., July 1, 2000; 56(1): 133 - 140. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. J. Eickholt, F. S. Walsh, and P. Doherty An inactive pool of GSK-3 at the leading edge of growth cones is implicated in Semaphorin 3A signaling J. Cell Biol., April 15, 2002; 157(2): 211 - 217. [Abstract] [Full Text] [PDF] |
||||