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Clostridium difficile toxin B, an inhibitor of the small GTPases Rho, Rac and Cdc42, influences spiral ganglion neurite outgrowth

Brors, Dominik and Aletsee, Christoph and Dazert, Stefan and Huverstuhl, Jochen and Ryan, Allen F. and Bodmer, Daniel. (2003) Clostridium difficile toxin B, an inhibitor of the small GTPases Rho, Rac and Cdc42, influences spiral ganglion neurite outgrowth. Acta oto-laryngologica, Vol. 123, no. 1. pp. 20-25.

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Official URL: http://edoc.unibas.ch/dok/A5252072

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Abstract

OBJECTIVE: Neurotrophins and extracellular matrix (ECM) molecules are involved in neurite guidance during the development of spiral ganglion (SG) neurons. Several intracellular signaling molecules can be activated by ECMs and neurotrophins via their cognate receptors. In other systems these include the Rho small GTPases, which influence reorganization of the actin cytoskeleton that is required for axon growth. The aim of this study was to determine whether neurotrophin-3 (NT-3)-mediated SG neurite outgrowth on laminin-1 (LN) is dependent on the activation of the small GTPases Rho/Rac/Cdc42. MATERIAL AND METHODS: SG explants from postnatal day 4 rats were cultured on LN with and without NT-3 and increasing concentrations of Clostridium difficile Toxin B, an inhibitor of Rho GTPases. After fixation and immunocytochemical labeling, neurite growth was evaluated. RESULTS: Treatment with C. difficile Toxin B without NT-3 led to a dose-dependent decrease in the length and number of processes on LN. In contrast, C. difficile Toxin B had no significant effect on NT-3-mediated stimulation of neurite growth on LN, in terms of either number or length. CONCLUSION: The results suggest that the Rho GTPases (Rho, Rac and Cdc42) are not involved in the pathways linking NT-3 signals to neurite outgrowth, but appear to be involved in LN signaling in these neurons. However, NT-3 can override or bypass LN signaling to promote neurite extension.
Faculties and Departments:03 Faculty of Medicine > Bereich Spezialf├Ącher (Klinik) > Otorhinolaryngologie > Oto-Rhino-Laryngologie (Bodmer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Spezialf├Ącher (Klinik) > Otorhinolaryngologie > Oto-Rhino-Laryngologie (Bodmer)
UniBasel Contributors:Bodmer, Daniel K
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Marcus
ISSN:0001-6489
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:24
Deposited On:22 Mar 2012 13:38

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