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.
References
Apr 15, 1992·Biochemical Pharmacology·E Enan, F Matsumura
Sep 2, 1991·Cell·J LiuS L Schreiber
Apr 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·D LipscombeR W Tsien
Dec 1, 1980·The Journal of Cell Biology·R W Gundersen, J N Barrett
Aug 1, 1994·The Journal of Cell Biology·K JalinkW H Moolenaar
Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·K K WangP Yuen
Jan 1, 1996·Journal of Neurobiology·T M GomezP C Letourneau
Jul 17, 1997·Nature·H J SongM M Poo
Jul 29, 1998·The Journal of Physiology·J ChurchJ G McLarnon
Oct 14, 1998·Developmental Biology·K Nakamoto, T Shiga
Jan 19, 2000·Nature·K HongM Poo
Oct 24, 2001·The Journal of Cell Biology·D M Suter, P Forscher
Apr 20, 2002·The Journal of Biological Chemistry·Sucheta KulkarniJoan E B Fox
Oct 23, 2002·Journal of Neurochemistry·Gary Meyer, Eva L Feldman
May 27, 2003·Neuron·Estuardo RoblesTimothy M Gomez
Oct 15, 2003·Neuron·Erik W Dent, Frank B Gertler
Sep 28, 2004·Nature Cell Biology·Santos J FrancoAnna Huttenlocher
Dec 18, 2004·Neuron·John R HenleyMu-ming Poo
Mar 5, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ming JinXiao-bing Yuan
Mar 11, 2005·Nature·Gordon X Wang, Mu-Ming Poo
May 10, 2005·Nature Neuroscience·Sangwoo ShimGuo-li Ming
Jan 24, 2006·Nature Reviews. Neuroscience·Timothy M Gomez, James Q Zheng
Mar 28, 2006·Neuroscience·K C W ToT P O'Connor
May 26, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Bridget T Jacques-FrickeTimothy M Gomez
May 26, 2006·Journal of Cell Science·Yolanda CalleGareth E Jones
Sep 11, 2007·Molecular and Cellular Neurosciences·Kenneth C W ToTimothy P O'Connor
Citations
Jul 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Qingyu QinXiaoning Bi
Apr 2, 2011·The Journal of Biological Chemistry·Yingchun WangRichard L Klemke
Feb 3, 2009·PloS One·Ana Mingorance-Le MeurTimothy P O'Connor
Aug 27, 2013·PloS One·Bérangère DelegliseJean-Michel Peyrin
Oct 21, 2009·Marine Drugs·Janice R SufrinColin M Oliver
May 17, 2014·Cell Death & Disease·J C KochP Lingor
May 25, 2012·The FEBS Journal·Astrid RohrbeckIngo Just
Feb 20, 2009·Biochemistry·Christopher P GarnhamPeter L Davies