BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery

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

Research output: Contribution to journalArticle

27 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)563-577
Number of pages15
JournalJournal of Cell Biology
Issue number4
StatePublished - 2015

ASJC Scopus subject areas

  • Cell Biology

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    Dennis, M. K., Mantegazza, A. R., Snir, O. L., Tenza, D., Acosta-Ruiz, A., Delevoye, C., Zorger, R., Sitaram, A., de Jesus-Rojas, W., Ravichandran, K., Rux, J., Sviderskaya, E. V., Bennett, D. C., Raposo, G., Marks, M. S., & Setty, S. R. G. (2015). BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery. Journal of Cell Biology, 209(4), 563-577.