Fig. P1.

(A) The cartoon depicts how dsu restores the coat color of dilute mice without restoring the defect in intracellular melanosome distribution with dilute melanocytes (keratinocytes are shaded yellow). Representative examples of pigment distribution and melanocyte shape (red signal) in ear skin are shown also. (B) (Left) Schematic of the proposed mechanism of melanosome transfer as gleaned from time-lapse imaging of melanocyte (MC)/keratinocyte (KC) cocultures in which the plasma membranes of these cells are red and green, respectively. Transfer involves adhesion between the side or tip of the MC’s dendrite and the surface of the KC, thinning of the MC’s dendrite behind the site of contact, an apparent self-abscission event in which the MC sheds a plasma membrane-enclosed package containing multiple melanosomes, and the eventual uptake of the package by the KC via phagocytosis. The internalized package appears as a cluster of black melanosomes surrounded by a red membrane (the remnants of the MC’s plasma membrane) that in turn is surrounded by a green membrane (the phagosomal membrane derived from the KC’s plasma membrane). (Right) Representative video frames for each step. Because melanoregulin negatively regulates this shedding mechanism, the dsu mutation increases melanosome transfer on both WT and dilute backgrounds.