Cédric Delevoye

Jeudi 29 mars 2018 à 11H30
Institut Curie
"The biogenesis of melanosomes: from intracellular trafficking to pigmentary disorders"
Invité par : Alexandra Rebsam

 Human skin and hair color relies on the production of melanin pigments by epidermal melanocytes. Melanin is synthesized and stored in melanosomes and photo-protects the skin against harmful ultra-violet solar radiation. Melanosomes are Lysosome-Related Organelles (LROs), but co-exist with conventional lysosomes. How specialized cell types, like melanocytes, have adapted their intracellular trafficking pathways to generate and maintain particular organelles such as the melanosomes is still incompletely understood.
Over the last decade, key trafficking steps of the melanocytes have been deciphered to provide a conceptual model, by which melanosomes are generated. Melanosomes originate from the endocytic pathway and progressively mature to develop into pigment granules through the proper endosomal sorting, packaging and transport of specific integral membrane proteins. These steps depend on the activity of ubiquitously expressed gene products named Biogenesis of LROs Complex (BLOC)-1, -2 and -3. These genes are mutated in the Hermansky-Pudlak Syndrome (HPS), a group of genetically heterogeneous disorders that is mainly characterized by OculoCutaneous Albinism (OCA), excessive bleeding and, in some cases, lung fibrosis that can lead to death in midlife. The OCA makes patients more susceptible to skin and ocular cancers and legally blind.
Recent studies reveal how BLOCs control the formation and maturation of melanosomes by specifying the endosome-to-melanosome trafficking route. Such work sheds new light on endosomal dynamics and their functions in virtually all cells, including neuronal cells. Indeed, some BLOC(s)-associated subunits could represent schizophrenia susceptibility factors. Therefore, the understanding of the cellular and molecular functions of those complexes might reveal how their associated defects underlie the pathophysiology of pigmentary and/ or neurological disorders.

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