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Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes
Cell types that generate unique lysosome-related organelles (LROs), such as melanosomes in melanocytes, populate nascent LROs with cargoes that are diverted from endosomes. Cargo sorting toward melanosomes correlates with binding via cytoplasmically exposed sorting signals to either heterotetrameric...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418312/ https://www.ncbi.nlm.nih.gov/pubmed/22718909 http://dx.doi.org/10.1091/mbc.E11-06-0509 |
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author | Sitaram, Anand Dennis, Megan K. Chaudhuri, Rittik De Jesus-Rojas, Wilfredo Tenza, Danièle Setty, Subba Rao Gangi Wood, Christopher S. Sviderskaya, Elena V. Bennett, Dorothy C. Raposo, Graça Bonifacino, Juan S. Marks, Michael S. |
author_facet | Sitaram, Anand Dennis, Megan K. Chaudhuri, Rittik De Jesus-Rojas, Wilfredo Tenza, Danièle Setty, Subba Rao Gangi Wood, Christopher S. Sviderskaya, Elena V. Bennett, Dorothy C. Raposo, Graça Bonifacino, Juan S. Marks, Michael S. |
author_sort | Sitaram, Anand |
collection | PubMed |
description | Cell types that generate unique lysosome-related organelles (LROs), such as melanosomes in melanocytes, populate nascent LROs with cargoes that are diverted from endosomes. Cargo sorting toward melanosomes correlates with binding via cytoplasmically exposed sorting signals to either heterotetrameric adaptor AP-1 or AP-3. Some cargoes bind both adaptors, but the relative contribution of each adaptor to cargo recognition and their functional interactions with other effectors during transport to melanosomes are not clear. Here we exploit targeted mutagenesis of the acidic dileucine–based sorting signal in the pigment cell–specific protein OCA2 to dissect the relative roles of AP-1 and AP-3 in transport to melanosomes. We show that binding to AP-1 or AP-3 depends on the primary sequence of the signal and not its position within the cytoplasmic domain. Mutants that preferentially bound either AP-1 or AP-3 each trafficked toward melanosomes and functionally complemented OCA2 deficiency, but AP-3 binding was necessary for steady-state melanosome localization. Unlike tyrosinase, which also engages AP-3 for optimal melanosomal delivery, both AP-1– and AP-3–favoring OCA2 variants required BLOC-1 for melanosomal transport. These data provide evidence for distinct roles of AP-1 and AP-3 in OCA2 transport to melanosomes and indicate that BLOC-1 can cooperate with either adaptor during cargo sorting to LROs. |
format | Online Article Text |
id | pubmed-3418312 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-34183122012-10-30 Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes Sitaram, Anand Dennis, Megan K. Chaudhuri, Rittik De Jesus-Rojas, Wilfredo Tenza, Danièle Setty, Subba Rao Gangi Wood, Christopher S. Sviderskaya, Elena V. Bennett, Dorothy C. Raposo, Graça Bonifacino, Juan S. Marks, Michael S. Mol Biol Cell Articles Cell types that generate unique lysosome-related organelles (LROs), such as melanosomes in melanocytes, populate nascent LROs with cargoes that are diverted from endosomes. Cargo sorting toward melanosomes correlates with binding via cytoplasmically exposed sorting signals to either heterotetrameric adaptor AP-1 or AP-3. Some cargoes bind both adaptors, but the relative contribution of each adaptor to cargo recognition and their functional interactions with other effectors during transport to melanosomes are not clear. Here we exploit targeted mutagenesis of the acidic dileucine–based sorting signal in the pigment cell–specific protein OCA2 to dissect the relative roles of AP-1 and AP-3 in transport to melanosomes. We show that binding to AP-1 or AP-3 depends on the primary sequence of the signal and not its position within the cytoplasmic domain. Mutants that preferentially bound either AP-1 or AP-3 each trafficked toward melanosomes and functionally complemented OCA2 deficiency, but AP-3 binding was necessary for steady-state melanosome localization. Unlike tyrosinase, which also engages AP-3 for optimal melanosomal delivery, both AP-1– and AP-3–favoring OCA2 variants required BLOC-1 for melanosomal transport. These data provide evidence for distinct roles of AP-1 and AP-3 in OCA2 transport to melanosomes and indicate that BLOC-1 can cooperate with either adaptor during cargo sorting to LROs. The American Society for Cell Biology 2012-08-15 /pmc/articles/PMC3418312/ /pubmed/22718909 http://dx.doi.org/10.1091/mbc.E11-06-0509 Text en © 2012 Sitaram et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Sitaram, Anand Dennis, Megan K. Chaudhuri, Rittik De Jesus-Rojas, Wilfredo Tenza, Danièle Setty, Subba Rao Gangi Wood, Christopher S. Sviderskaya, Elena V. Bennett, Dorothy C. Raposo, Graça Bonifacino, Juan S. Marks, Michael S. Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes |
title | Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes |
title_full | Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes |
title_fullStr | Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes |
title_full_unstemmed | Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes |
title_short | Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes |
title_sort | differential recognition of a dileucine-based sorting signal by ap-1 and ap-3 reveals a requirement for both bloc-1 and ap-3 in delivery of oca2 to melanosomes |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418312/ https://www.ncbi.nlm.nih.gov/pubmed/22718909 http://dx.doi.org/10.1091/mbc.E11-06-0509 |
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