Structure and Membrane Compartments

 

In the skin epidermis, pigmented melanocytes contact and communicate with neighboring keratinocytes. Within the melanocyte, the pigment melanin is synthesized and stored in an organelle, the melanosome.

 

In the epidermis, the thin outermost layer of the skin, melanocytes in close contact with keratinocytes form the so-called epidermal-melanin unit. There, melanocytes synthesize the pigment melanin in lysosome-related organelles called melanosomes that are further transferred to keratinocytes in order to color the skin and to provide photo-protection against UV solar radiations. Melanocytes and keratinocytes communicate by direct contacts as well as the release of soluble factors and of Extracellular Vesicles, like exosomes. Such intercellular communication is crucial to regulate the biogenesis of melanosomes, their transfer to keratinocytes, as well as their fate in keratinocytes. All these processes and the involved components are thus key to dictate the pigmentation status of the skin, its capacity to photo-protect, and can be targeted in inherited pigmentary disorders, like albinisms and skin cancers.

The endosomal system is a network of organelles with essential roles in eukaryotic cells for physiological processes such as nutrient uptake, macromolecule degradation and signaling. Some specialized-cell types adapt the endocytic pathway to generate unique organelles sharing features with lysosomes, the lysosome-related organelles (LROs). Several genetic diseases and cell transformation are accompanied by malformation and malfunction of LROs. Among LROs, we focus on the melanosomes, the pigment granules produced by epidermal melanocytes and transferred to keratinocytes to photoprotect the skin against the harmful effect of the UV solar radiations. We investigate the cellular and molecular mechanisms involved in the biogenesis and function of melanosomes in melanocytes and keratinocytes, and their alterations in diseases. Another functional modulation of the endocytic pathway is highlighted by the secretory capacity of multivesicular endosomes, or multivesicular bodies (MVBs), that release in the extracellular space their intraluminal vesicles, called exosomes. Endosome-derived exosomes, together with other extracellular vesicles generated from the plasma membrane and called microvesicles, contain proteins, lipids and genetic materials. They play key roles in cell-to-cell communication in health and disease. Our studies exploit a variety of human cell lines, primary cells and tissues by developing state of the art electron microscopical methods combined with light microscopy, cell and molecular biology and biochemistry.