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

Dennis, Megan K and Mantegazza, Adriana R and Snir, Olivia L and Tenza, Daniele and Acosta-Ruiz, Amanda and Delevoye, Cedric and Zorger, Richard and Sitaram, Anand and de Jesus-Rojas, Wilfredo and Ravichandran, Keerthana and Rux, John and Sviderskaya, Elena V and Bennett, Dorothy C and Raposo, Graca and Marks, Michael S and Setty, Subba Rao Gangi (2015) BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery. In: JOURNAL OF CELL BIOLOGY, 209 (4). pp. 563-577.

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Abstract

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.

Item Type:	Journal Article
Publication:	JOURNAL OF CELL BIOLOGY
Publisher:	ROCKEFELLER UNIV PRESS
Additional Information:	Copy right for this article belongs to the ROCKEFELLER UNIV PRESS, 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	19 Jul 2015 09:20
Last Modified:	19 Jul 2015 09:20
URI:	http://eprints.iisc.ac.in/id/eprint/51823

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