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

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 thi...

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Autores principales: Dennis, Megan K., Mantegazza, Adriana R., Snir, Olivia L., Tenza, Danièle, Acosta-Ruiz, Amanda, Delevoye, Cédric, Zorger, Richard, Sitaram, Anand, de Jesus-Rojas, Wilfredo, Ravichandran, Keerthana, Rux, John, Sviderskaya, Elena V., Bennett, Dorothy C., Raposo, Graça, Marks, Michael S., Setty, Subba Rao Gangi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442807/
https://www.ncbi.nlm.nih.gov/pubmed/26008744
http://dx.doi.org/10.1083/jcb.201410026
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author Dennis, Megan K.
Mantegazza, Adriana R.
Snir, Olivia L.
Tenza, Danièle
Acosta-Ruiz, Amanda
Delevoye, Cédric
Zorger, Richard
Sitaram, Anand
de Jesus-Rojas, Wilfredo
Ravichandran, Keerthana
Rux, John
Sviderskaya, Elena V.
Bennett, Dorothy C.
Raposo, Graça
Marks, Michael S.
Setty, Subba Rao Gangi
author_facet Dennis, Megan K.
Mantegazza, Adriana R.
Snir, Olivia L.
Tenza, Danièle
Acosta-Ruiz, Amanda
Delevoye, Cédric
Zorger, Richard
Sitaram, Anand
de Jesus-Rojas, Wilfredo
Ravichandran, Keerthana
Rux, John
Sviderskaya, Elena V.
Bennett, Dorothy C.
Raposo, Graça
Marks, Michael S.
Setty, Subba Rao Gangi
author_sort Dennis, Megan K.
collection PubMed
description 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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spelling pubmed-44428072015-11-25 BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery Dennis, Megan K. Mantegazza, Adriana R. Snir, Olivia L. Tenza, Danièle Acosta-Ruiz, Amanda Delevoye, Cédric Zorger, Richard Sitaram, Anand de Jesus-Rojas, Wilfredo Ravichandran, Keerthana Rux, John Sviderskaya, Elena V. Bennett, Dorothy C. Raposo, Graça Marks, Michael S. Setty, Subba Rao Gangi J Cell Biol Research Articles 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. The Rockefeller University Press 2015-05-25 /pmc/articles/PMC4442807/ /pubmed/26008744 http://dx.doi.org/10.1083/jcb.201410026 Text en © 2015 Dennis et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Dennis, Megan K.
Mantegazza, Adriana R.
Snir, Olivia L.
Tenza, Danièle
Acosta-Ruiz, Amanda
Delevoye, Cédric
Zorger, Richard
Sitaram, Anand
de Jesus-Rojas, Wilfredo
Ravichandran, Keerthana
Rux, John
Sviderskaya, Elena V.
Bennett, Dorothy C.
Raposo, Graça
Marks, Michael S.
Setty, Subba Rao Gangi
BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery
title BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery
title_full BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery
title_fullStr BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery
title_full_unstemmed BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery
title_short BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery
title_sort bloc-2 targets recycling endosomal tubules to melanosomes for cargo delivery
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442807/
https://www.ncbi.nlm.nih.gov/pubmed/26008744
http://dx.doi.org/10.1083/jcb.201410026
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