RAC1 MEDIATES DENDRITE FORMATION IN RESPONSE TO MELANOCYTE-STIMULATING HORMONE AND ULTRAVIOLET-LIGHT IN A MURINE MELANOMA MODEL

Melanocytes are pigment producing cells that reside in the basal layer of the epidermis, and form multiple long dendritic processes that tra nsport melanosomes from the melanocyte cell body to the dendritic tips , and then to keratinocytes. Dendrite format-ion requires actin polyme rization in the newly forming dendrite, and dendrite formation in mela nocytes is stimulated by hormones and ultraviolet light. The rho-subfa mily of monomeric guanosine triphosphate-binding proteins is implicate d in remodeling the cellular actin cytoskeleton, resulting in the form ation of filopodia, lamellipodia, and stress fibers, as well as in onc ogenesis and activation of the Jun/p38 mitogen activated kinase cascad e, In this paper we show that rad induces the formation of dendrite-li ke structures when activated mutants are transiently expressed in B16F 1 murine melanoma cells and in four human melanoma cell lines. Activat ed mutants of cdc42 and rhoA induced the formation of filopodia and st ress fibers, respectively, in B16F1 cells, but not dendrites, A domina nt negative inhibitor of rad abrogated the ability of alpha-melanocyte stimulating hormone, a peptide hormone known to stimulate melanocyte dendrite formation, and ultraviolet light, to induce dendrite formatio n in B16F1 cells, and alpha-melanocyte stimulating hormone and ultravi olet light stimulated the localization of rad to dendrite cell membran es, These results suggest that rad is an important signaling intermedi ate in dendrite formation in B16F1 cells, and that rac1 mediates the w ell-known ability of alpha-melanocyte stimulating hormone and ultravio let light to induce dendrite formation.