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The small GTP-binding proteins, Rac and Rho, regulate cytoskeletal organization and exocytosis in mast cells by
J C Norman1, L S Price, A J Ridley
1Physiology Department, University College London, United Kingdom.
Molecular Biology of the Cell
|September 1, 1996
Summary
Mast cell secretion involves actin reorganization regulated by GTP-binding proteins like Rac and Rho. These proteins control secretion and cytoskeletal changes through parallel signaling pathways, not a single shared one.
Area of Science:
- Cell Biology
- Molecular Biology
Background:
- GTP-binding proteins, specifically Rac and Rho, are crucial for mast cell activation, influencing actin filament reorganization and secretory functions.
- Mast cell secretion is a complex process, and the precise signaling pathways linking cytoskeletal dynamics to exocytosis remain under investigation.
Purpose of the Study:
- To investigate the relationship between actin organization and secretory response in mast cells.
- To elucidate the roles of Rac and Rho GTPases in controlling both cytoskeletal and secretory functions.
- To determine if Rac and Rho utilize shared or divergent signaling pathways for these cellular processes.
Main Methods:
- Comparison of actin organization in secreting versus non-secreting permeabilized mast cells.
- Inhibition of actin relocalization and polymerization using phalloidin and cytochalasin, respectively.
- Assessment of secretory function in the presence of constitutively active Rac and Rho mutants and inhibitors.
Main Results:
- A strong correlation exists between cytoskeletal and secretory responses, suggesting a common upstream regulator.
- Secreting mast cells exhibit preferential actin relocalization and polymerization.
- Inhibition of actin relocalization or polymerization does not affect secretion, and Rac/Rho mutants enhance secretion independently of actin polymerization.
Conclusions:
- Rac and Rho GTPases regulate mast cell secretion and actin dynamics through divergent, parallel signaling pathways.
- Cortical actin disassembly occurs in both secreting and non-secreting cells and is not sufficient to induce exocytosis.
- A model involving at least four GTP-binding proteins is proposed, highlighting shared and divergent pathways from Rac and Rho in exocytosis control.