FIG 9.

Model for the role of mDia1 in coordinating MC migration and secretion. According to our proposed model, MC activation by IL-8 involves activation of RhoA, which in turn binds to and relieves mDia1 from its autoinhibited state (Closed IA converted to Open IA). Another yet unknown modification is required that can be transduced by either IL-8 or FcεRI signaling to achieve full activation of mDia1 (Open IA converted to mDia1-X Open A). Through its actin-polymerizing activity, mDia1 then builds up the pericentral actin clusters that prevent cell flattening and converge the SGs, thereby inhibiting their release. When IL-8-stimulated cells are exposed to FcεRI signaling, the latter inhibits RhoA activation, thereby reverting mDia1 to its autoinhibited state. Therefore the secretory signal overrides the migratory signal, which is elicited by the chemokine receptor.