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Role of AP1 and Gadkin in the traffic of secretory endo-lysosomes

Whereas lysosome-related organelles (LRO) of specialized cells display both exocytic and endocytic features, lysosomes in nonspecialized cells can also acquire the property to fuse with the plasma membrane upon an acute rise in cytosolic calcium. Here, we characterize this unconventional secretory p...

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Autores principales: Laulagnier, Karine, Schieber, Nicole L., Maritzen, Tanja, Haucke, Volker, Parton, Robert G., Gruenberg, Jean
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113771/
https://www.ncbi.nlm.nih.gov/pubmed/21525240
http://dx.doi.org/10.1091/mbc.E11-03-0193
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author Laulagnier, Karine
Schieber, Nicole L.
Maritzen, Tanja
Haucke, Volker
Parton, Robert G.
Gruenberg, Jean
author_facet Laulagnier, Karine
Schieber, Nicole L.
Maritzen, Tanja
Haucke, Volker
Parton, Robert G.
Gruenberg, Jean
author_sort Laulagnier, Karine
collection PubMed
description Whereas lysosome-related organelles (LRO) of specialized cells display both exocytic and endocytic features, lysosomes in nonspecialized cells can also acquire the property to fuse with the plasma membrane upon an acute rise in cytosolic calcium. Here, we characterize this unconventional secretory pathway in fibroblast-like cells, by monitoring the appearance of Lamp1 on the plasma membrane and the release of lysosomal enzymes into the medium. After sequential ablation of endocytic compartments in living cells, we find that donor membranes primarily derive from a late compartment, but that an early compartment is also involved. Strikingly, this endo-secretory process is not affected by treatments that inhibit endosome dynamics (microtubule depolymerization, cholesterol accumulation, overexpression of Rab7 or its effector Rab-interacting lysosomal protein [RILP], overexpression of Rab5 mutants), but depends on Rab27a, a GTPase involved in LRO secretion, and is controlled by F-actin. Moreover, we find that this unconventional endo-secretory pathway requires the adaptor protein complexes AP1, Gadkin (which recruits AP1 by binding to the γ1 subunit), and AP2, but not AP3. We conclude that a specific fraction of the AP2-derived endocytic pathway is dedicated to secretory purposes under the control of AP1 and Gadkin.
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spelling pubmed-31137712011-08-30 Role of AP1 and Gadkin in the traffic of secretory endo-lysosomes Laulagnier, Karine Schieber, Nicole L. Maritzen, Tanja Haucke, Volker Parton, Robert G. Gruenberg, Jean Mol Biol Cell Articles Whereas lysosome-related organelles (LRO) of specialized cells display both exocytic and endocytic features, lysosomes in nonspecialized cells can also acquire the property to fuse with the plasma membrane upon an acute rise in cytosolic calcium. Here, we characterize this unconventional secretory pathway in fibroblast-like cells, by monitoring the appearance of Lamp1 on the plasma membrane and the release of lysosomal enzymes into the medium. After sequential ablation of endocytic compartments in living cells, we find that donor membranes primarily derive from a late compartment, but that an early compartment is also involved. Strikingly, this endo-secretory process is not affected by treatments that inhibit endosome dynamics (microtubule depolymerization, cholesterol accumulation, overexpression of Rab7 or its effector Rab-interacting lysosomal protein [RILP], overexpression of Rab5 mutants), but depends on Rab27a, a GTPase involved in LRO secretion, and is controlled by F-actin. Moreover, we find that this unconventional endo-secretory pathway requires the adaptor protein complexes AP1, Gadkin (which recruits AP1 by binding to the γ1 subunit), and AP2, but not AP3. We conclude that a specific fraction of the AP2-derived endocytic pathway is dedicated to secretory purposes under the control of AP1 and Gadkin. The American Society for Cell Biology 2011-06-15 /pmc/articles/PMC3113771/ /pubmed/21525240 http://dx.doi.org/10.1091/mbc.E11-03-0193 Text en © 2011 Laulagnier 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 Biology.
spellingShingle Articles
Laulagnier, Karine
Schieber, Nicole L.
Maritzen, Tanja
Haucke, Volker
Parton, Robert G.
Gruenberg, Jean
Role of AP1 and Gadkin in the traffic of secretory endo-lysosomes
title Role of AP1 and Gadkin in the traffic of secretory endo-lysosomes
title_full Role of AP1 and Gadkin in the traffic of secretory endo-lysosomes
title_fullStr Role of AP1 and Gadkin in the traffic of secretory endo-lysosomes
title_full_unstemmed Role of AP1 and Gadkin in the traffic of secretory endo-lysosomes
title_short Role of AP1 and Gadkin in the traffic of secretory endo-lysosomes
title_sort role of ap1 and gadkin in the traffic of secretory endo-lysosomes
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113771/
https://www.ncbi.nlm.nih.gov/pubmed/21525240
http://dx.doi.org/10.1091/mbc.E11-03-0193
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