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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2015
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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. |
format | Online Article Text |
id | pubmed-4442807 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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