Rho Controls Cortical F-actin Disassembly in Addition to, but Independently of, Secretion in Mast Cells
Localized 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...
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Veröffentlicht in: | The Journal of biological chemistry 1999-12, Vol.274 (53), p.38140-38146 |
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Zusammenfassung: | Localized 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 (â¼80%)
and F-actin disassembly (â¼20%). 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. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.274.53.38140 |