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 transport melanosomes from the melanocyte cell body to the dendritic tips, and then to keratinocytes. Dendrite formation requires actin polymerization in the newly forming dendrite, and dendrite formation in melanocytes is stimulated by hormones and ultraviolet light. The rho-subfamily of monomeric guanosine triphosphate-binding proteins is implicated in remodeling the cellular actin cytoskeleton, resulting in the formation of filopodia, lamellipodia, and stress fibers, as well as in oncogenesis and activation of the Jun/p38 mitogen activated kinase cascade. In this paper we show that rac1 induces the formation of dendrite-like structures when activated mutants are transiently expressed in B16F1 murine melanoma cells and in four human melanoma cell lines. Activated mutants of cdc42 and rhoA induced the formation of filopodia and stress fibers, respectively, in B16F1 cells, but not dendrites. A dominant negative inhibitor of rac1 abrogated the ability of alpha-melanocyte stimulating hormone, a peptide hormone known to stimulate melanocyte dendrite formation, and ultraviolet light, to induce dendrite formation in B16F1 cells, and alpha-melanocyte stimulating hormone and ultraviolet light stimulated the localization of rac1 to dendrite cell membranes. These results suggest that rac1 is an important signaling intermediate in dendrite formation in B16F1 cells, and that rac1 mediates the well-known ability of alpha-melanocyte stimulating hormone and ultraviolet light to induce dendrite formation.
Department of Dermatology, University of Rochester Medical Center, New York 14642, USA.
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D000199:Actins / Q000032:analysis; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D011817:Rabbits; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D020744:rac GTP-Binding Proteins
D000199:Actins; D009074:Melanocyte-Stimulating Hormones; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins; D002118:Calcium