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

Laulagnier, Karine, Schieber, Nicole L., Maritzen, Tanja, Haucke, Volker, Parton, Robert G. and Gruenberg, Jean (2011) Role of AP1 and Gadkin in the traffic of secretory endo-lysosomes. Molecular Biology of the Cell, 22 12: 2068-2082. doi: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
Title Role of AP1 and Gadkin in the traffic of secretory endo-lysosomes
Journal name Molecular Biology of the Cell   Check publisher's open access policy
ISSN 1059-1524
Publication date 2011-06-15
Sub-type Article (original research)
DOI 10.1091/mbc.E11-03-0193
Open Access Status File (Publisher version)
Volume 22
Issue 12
Start page 2068
End page 2082
Total pages 15
Place of publication Bethesda, MD, United States
Publisher American Society for Cell Biology
Collection year 2012
Language eng
Abstract 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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Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
Institute for Molecular Bioscience - Publications
Centre for Microscopy and Microanalysis Publications
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Citation counts: TR Web of Science Citation Count  Cited 20 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 24 Feb 2012, 15:45:18 EST by Susan Allen on behalf of Institute for Molecular Bioscience