Configuration of human dendritic cell cytoskeleton by Rho GTPases, the WASprotein, and differentiation

The cellular mechanisms that configure the cytoskeleton during migration of dendritic cells (DCs) are poorly understood. Immature DCs assemble special ized adhesion structures known as podosomes at their leading edge; these ar e associated with the localized recruitment of the Wiskott-Aldrich Syndrome protein (WASp) and the actin organizing actin-related protein 2/3 complex. In immature DCs lacking WASp, podosomes are absent, residual dysmorphic la mellipodia and filopodia are nonpolarized, and migration is severely compro mised. Microinjection studies indicate that podosome assembly and polarizat ion require concerted action of Cdc42, Rac, and Rho, thereby providing a li nk between sequential protrusive and adhesive activity. Formation of podoso mes is restricted to cells with an immature phenotype, indicating a specifi c role for these structures during the early migratory phase.