Linked Life Data

10608885

Source:http://linkedlifedata.com/resource/pubmed/id/10608885

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pubmed-article:10608885pubmed:abstractTextLocalized disassembly of cortical F-actin has long been considered necessary for facilitation of exocytosis. Exposure of permeabilized mast cells to calcium/ATP induces cortical F-actin disassembly (calmodulin-dependent) and secretion (calmodulin-independent). The delay in the onset of secretion is characteristic for the calcium/ATP response and is abolished by GTP. Here we report that a constitutively active mutant of Rho (V14RhoA) enhanced both secretion and cortical F-actin disassembly. In addition, V14RhoA mimicked GTP by abolishing the delay in secretion. Inhibition of Rho by C3 transferase prevented both secretion ( approximately 80%) and F-actin disassembly (approximately 20%). Thus, both Rho GTPase and calcium/calmodulin contribute to the control of cortical F-actin disassembly. Stabilization of actin filaments by high concentrations of phalloidin or by a calmodulin-inhibitory peptide (based on the calmodulin-binding domain of myosin light chain kinase) did not affect the extent of secretion or the secretion-enhancing effects of V14RhoA. These results further support the existence of divergent, Rho-dependent, pathways regulating actin and exocytosis. Furthermore, compound Y-27632, a specific inhibitor of Rho-associated protein kinase (p160(ROCK)), attenuated the Rho-induced loss of cortical F-actin without affecting secretion. A model is presented in which Rho regulates secretion and cortical F-actin in a manner dependent on and/or synergistic with calcium.lld:pubmed
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pubmed-article:10608885pubmed:dateRevised2007-11-15lld:pubmed
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pubmed-article:10608885pubmed:articleTitleRho controls cortical F-actin disassembly in addition to, but independently of, secretion in mast cells.lld:pubmed
pubmed-article:10608885pubmed:affiliationPhysiology Department, University College London, University Street, London WC1E 6JJ, United Kingdom.lld:pubmed
pubmed-article:10608885pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:10608885pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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