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The anti-invasive compound motuporamine C is a robust stimulator of neuronal growth cone collapse

TitleThe anti-invasive compound motuporamine C is a robust stimulator of neuronal growth cone collapse
Publication TypeJournal Article
Year of Publication2006
AuthorsTo, KCW, Loh, KT, Roskelley, CD, Andersen, RJ, O’Connor, TP
JournalNeuroscience
Volume139
Pagination1263-1274
Type of ArticleArticle
ISBN Number0306-4522
KeywordsACTIN STRESS FIBERS, ADP-RIBOSYLATION, AXONAL GROWTH, BINDING PROTEIN-RHO, collapse, development, FOCAL ADHESIONS, growth cone, IN-VIVO, KINASE-ACTIVITY, LYSOPHOSPHATIDIC ACID, motuporamine, NEURITE RETRACTION, outgrowth, RECEPTORS, Rho GTPase
Abstract

Neuronal outgrowth is a fundamental process for normal development of the nervous system. Despite recent advances, the molecular mechanisms governing neuronal motility are still poorly understood. To provide insight into the intracellular signaling mechanisms required for neuronal outgrowth, we have characterized the effects of a compound previously identified for its anti-motility effects on transformed cells. We show that this compound, motuporamine C, acts as a robust inhibitor of chick neurite outgrowth in a dose-dependent fashion. Furthermore, in the presence of motuporamine C, growth cone collapse is observed, followed by neurite retraction. After removal, growth cones re-extend lamellipodial and filopodial processes and re-establish motility. Neurons exposed to motuporamine C exhibit a significant upregulation of active Rho-GTP. Additionally, effector-blocking experiments using Rho and Rho-associated kinase inhibitors indicate that the Rho pathway plays a critical role in motuporamine C-mediated growth cone collapse. Thus, we have characterized a novel anti-motility compound that has a robust inhibitory effect on neuronal outgrowth and involves signaling through the Rho-Rho kinase collapse pathway. Due to these robust effects, motuporamine C may serve as a valuable tool in further examining the intracellular mechanisms associated with growth cone motility. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.

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