Growth cone collapse stimulated by both calpain- and Rho-mediated pathways

Neuroscience
K C W ToT P O'Connor

Abstract

The signal transduction pathways regulating growth cone motility remain poorly defined. Previously, we have characterized the inhibitory molecule, motuporamine C (MotC), as a robust stimulator of growth cone collapse. Utilizing MotC as a research tool to elucidate pathways involved with collapse, we have previously shown that the Rho-Rho kinase (ROCK) pathway is partially required for collapse. In this study, we report MotC induces a high-amplitude rise in intracellular free Ca(2+) concentration levels in chicks, resulting in the activation of the Ca(2+)-sensitive protease, calpain. Furthermore, we show that while calpain is necessary for collapse, inhibition of calpain only partially attenuates MotC-mediated collapse. Instead, concomitant inhibition of both the Rho-ROCK and calpain pathways has an additive effect in attenuating the collapse response to MotC. To our knowledge, this is the first demonstration of concurrent activation of calpain and Rho-ROCK signaling during growth cone collapse. Our data support a model of growth cone collapse that requires the combinatorial regulation of multiple signal transduction cascades that likely target different cellular mechanisms to induce this motile response.

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Citations

Jul 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Qingyu QinXiaoning Bi
Feb 3, 2009·PloS One·Ana Mingorance-Le MeurTimothy P O'Connor
Aug 27, 2013·PloS One·Bérangère DelegliseJean-Michel Peyrin
May 25, 2012·The FEBS Journal·Astrid RohrbeckIngo Just

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