Brown, M.;
Jacobs, T.;
Eickholt, B.;
Ferrari, G.;
Teo, M.;
Monfries, C.;
Qi, R.Z.;
... Hall, C.; + view all
(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.
Journal of Neuroscience
, 24
(41)
pp. 8994-9004.
10.1523/JNEUROSCI.3184-04.2004.
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Abstract
Neurite outgrowth is influenced by positive and negative signals that include the semaphorins, an important family of axonal outgrowth inhibitors. Here we report that the Rac GTPase activating protein (GAP){alpha}2-chimaerin is involved in Semaphorin 3A (Sema 3A) signaling. In dorsal root ganglion neurons, Sema 3A-induced growth cone collapse was inhibited by {alpha}2-chimaerin mutated to eliminate GAP activity or interaction with phosphotyrosine. Activation of {alpha}2-chimaerin by phorbol ester caused growth cone collapse. Active {alpha}2-chimaerin interacts with collapsin response mediator protein-2 (CRMP-2) and cyclin-dependent kinase (Cdk) 5/p35 kinase through its SH2 and GAP domains, respectively. Cdk5 phosphorylates CRMP-2 at serine 522, possibly facilitating phosphorylation of serine 518 and threonine 514 by glycogen synthase kinase 3{beta} (GSK3{beta}), a kinase previously implicated in Sema 3A signaling. Phosphorylation of CRMP-2 serine 522 was essential for Sema 3A-induced growth cone collapse, which is dependent on Cdk5 but not Rho kinase activity. {alpha}2-chimaerin, like CRMP-2, can associate with the Sema 3A receptor. These results indicate that active {alpha}2-chimaerin Rac GAP, Cdk5/p35, and its substrate CRMP-2, are implicated in the dynamics of growth cone guidance initiated through Sema 3A signaling.
| Type: | Article |
|---|---|
| Title: | {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 |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1523/JNEUROSCI.3184-04.2004 |
| Publisher version: | http://dx.doi.org/10.1523/JNEUROSCI.3184-04.2004 |
| Language: | English |
| Additional information: | Copyright Society for Neuroscience 2004 This work is licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. The license allows you to copy, distribute, and transmit the work, as well as adapting it. However, you must attribute the work to the author (but not in any way that suggests that they endorse you or your use of the work), and cannot use the work for commercial purposes without prior permission of the author. If you alter or build upon this work, you can distribute the resulting work only under the same or similar license to this one. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ or send a letter to Creative Commons, 444 Castro Street, Suite 900, Mountain View, California, 94041, USA. |
| Keywords: | Sema 3A, RacGTPase, CRMP-2, {alpha}2-chimaerin, Cdk5/p35, growth cone collapse |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/7411 |
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