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- BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery
BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery
Auteurs
Megan K. Dennis, Adriana R. Mantegazza, Olivia L. Snir, Danièle Tenza, Amanda Acosta-Ruiz, Cédric Delevoye, Richard Zorger, Anand Sitaram, Wilfredo de Jesus-Rojas, Keerthana Ravichandran, John Rux, Elena V. Sviderskaya, Dorothy C. Bennett, Graça Raposo, Michael S. Marks, Subba Rao Gangi Setty
Résumé
Hermansky–Pudlak syndrome (HPS) is a group of disorders characterized by the malformation of lysosome-related organelles, such as pigment cell melanosomes. Three of nine characterized HPS subtypes result from mutations in subunits of BLOC-2, a protein complex with no known molecular function. In this paper, we exploit melanocytes from mouse HPS models to place BLOC-2 within a cargo transport pathway from recycling endosomal domains to maturing melanosomes. In BLOC-2–deficient melanocytes, the melanosomal protein TYRP1 was largely depleted from pigment granules and underwent accelerated recycling from endosomes to the plasma membrane and to the Golgi. By live-cell imaging, recycling endosomal tubules of wild-type melanocytes made frequent and prolonged contacts with maturing melanosomes; in contrast, tubules from BLOC-2–deficient cells were shorter in length and made fewer, more transient contacts with melanosomes. These results support a model in which BLOC-2 functions to direct recycling endosomal tubular transport intermediates to maturing melanosomes and thereby promote cargo delivery and optimal pigmentation.
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