Growth cone collapse stimulated by both calpain- and Rho-mediated pathways.
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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KC
Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Church
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J
O'Connor
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TP
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002154:Calpain / Q000502:physiology*; D002642:Chick Embryo; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D054460:rho-Associated Kinases / Q000502:physiology*
D000470:Alkaloids; C409085:motuporamine C; D054460:rho-Associated Kinases; D002154:Calpain; D002118:Calcium