THE SMALL GTP-BINDING PROTEINS, RAC AND RHO, REGULATE CYTOSKELETAL ORGANIZATION AND EXOCYTOSIS IN MAST-CELLS BY PARALLEL PATHWAYS

In mast cells, activation of GTP-binding proteins induces centripetal reorganization of actin filaments. This effect is due to disassembly, relocalization, and polymerization of F-actin and is dependent on two small GTPases, Rac and Rho. Activities of Rac and Rho are also essenti al for the secretory function of mast cells. In response to GTP-gamma- S and/or calcium, only a proportion of permeabilized mast cells is cap able of secretory response. Here, we have compared actin organization of secreting and nonsecreting cell populations. We show that the cytos keletal and secretory responses are strongly correlated, indicating a common upstream regulator of the two functions. The secreting cell pop ulation preferentially displays both relocalization and-polymerization of actin. However, when actin relocalization or polymerization is inh ibited by phalloidin or cytochalasin, respectively, secretion is unaff ected. Moreover, the ability of the constitutively active mutants of R ac and Rho to enhance secretion is also unaffected in the presence of cytochalasin. Therefore, Rac and Rho control these two functions by di vergent, parallel signaling pathways. Cortical actin disassembly occur s in both secreting and nonsecreting populations and does not, by itse lf, induce exocytosis. A model for the control of exocytosis is propos ed that includes at least four GTP-binding proteins and suggests the p resence of both shared and divergent signaling pathways from Rac and R ho.