Rnd1 Regulates Axon Extension by Enhancing the Microtubule Destabilizing Activity of SCG10*
- Ying-Hua Li‡1,
- Sharang Ghavampur‡2,
- Percy Bondallaz§,
- Lena Will‡,
- Gabriele Grenningloh§3 and
- Andreas W. Püschel‡4
- ‡Abteilung Molekularbiologie, Institut für Allgemeine Zoologie und Genetik, Westfälische Wilhelms-Universität Münster, Schloßplatz 5, D-48149 Münster, Germany and the §Center for Psychiatric Neuroscience, Department of Psychiatry-Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1008 Prilly, Switzerland
- 4 To whom correspondence should be addressed: Abteilung Molekularbiologie, Institut für Allgemeine Zoologie und Genetik, Westfälische Wilhelms-Universität Münster, Schloßplatz 5, D-48149 Münster, Germany. E-mail: apuschel{at}uni-muenster.de.
Abstract
The GTPase Rnd1 affects actin dynamics antagonistically to Rho and has been implicated in the regulation of neurite outgrowth, dendrite development, and axon guidance. Here we show that Rnd1 interacts with the microtubule regulator SCG10. This interaction requires a central domain of SCG10 comprising about 40 amino acids located within the N-terminal-half of a putative α-helical domain and is independent of phosphorylation at the four identified phosphorylation sites that regulate SCG10 activity. Rnd1 enhances the microtubule destabilizing activity of SCG10 and both proteins colocalize in neurons. Knockdown of Rnd1 or SCG10 by RNAi suppressed axon extension, indicating a critical role for both proteins during neuronal differentiation. Overexpression of Rnd1 in neurons induces the formation of multiple axons. The effect of Rnd1 on axon extension depends on SCG10. These results indicate that SCG10 acts as an effector downstream of Rnd1 to regulate axon extensions by modulating microtubule organization.
Footnotes
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↵5 The abbreviations used are: SCG10, Superior Cervical Ganglion10; PBS, phosphate-buffered saline; CaMK, calcium/calmodulin-dependent protein kinase; GST, glutathione S-transferase; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; RNAi, RNA interference; DTT, dithiothreitol; GTPγS, guanosine 5′-3-O-(thio)triphosphate; Pipes, 1,4-piperazinediethanesulfonic acid; MES, 4-morpholineethanesulfonic acid.
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↵6 G. Grenningloh, unpublished results.
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↵* This work was supported by Deutsche Forschungsgemeinschaft Grants SFB 629 and SPP 1090 (to A. W. P.) and the Swiss National Science Foundation Grant 3100AO-10425 (to G. G.). 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.
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The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S3.
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↵1 Present address: Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, 3501 Fifth Ave., Pittsburgh, PA 15260.
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↵2 Present address: Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Münster, Von-Esmarch-Str. 56, D-48149 Münster, Germany.
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↵3 Present address: Ecole Polytechnique Fédérale de Lausanne, Brain Mind Institute, Station 19, 1015 Lausanne, Switzerland.
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- Received October 22, 2008.
- The American Society for Biochemistry and Molecular Biology, Inc.
