Shining a Light on Black Holes in Keratinocytes

Abstract

The mechanisms by which melanins are transferred from melanocytes and stored within keratinocytes to generate skin pigmentation are hotly debated. Correia et al. and Hurbain et al. provide evidence that melanin cores of melanosomes are secreted from melanocytes and taken up and stored within non-degradative membranous organelles in keratinocytes in the basal epidermis of human skin.

Figure 1. Melanocore uptake and storage by keratinocytes

Melanocores are secreted by melanocytes into the extracellular space and phagocytosed by keratinocytes (step 1). PAR2 signaling and Rab5 are required for melanocore phagocytosis (step 2). Melanocores in keratinocytes are stored in non-degradative compartments bounded by single membranes that contain CD63 and LAMP2 and that contact rough and smooth ER, mitochondria, and small tubular membranes of unknown origin (step 3). These compartments harbor either clustered structures or dense, isolated structures in all skin types, but the ratio of clustered to isolated melanocore structures decreases as skin pigmentation increases (step 3, top vs. bottom). Although it is not yet clear how melanin storage organelles in keratinocytes mature, some clustered melanocores in lightly pigmented skin may undergo partial degradation (steps 2 to 3).