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Mammalian GGAs act together to sort mannose 6-phosphate receptors
The GGAs (Golgi-localized, γ ear–containing, ADP ribosylation factor–binding proteins) are multidomain proteins implicated in protein trafficking between the Golgi and endosomes. We examined whether the three mammalian GGAs act independently or together to mediate their functions. Using cryo-immunog...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173681/ https://www.ncbi.nlm.nih.gov/pubmed/14638859 http://dx.doi.org/10.1083/jcb.200308038 |
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author | Ghosh, Pradipta Griffith, Janice Geuze, Hans J. Kornfeld, Stuart |
author_facet | Ghosh, Pradipta Griffith, Janice Geuze, Hans J. Kornfeld, Stuart |
author_sort | Ghosh, Pradipta |
collection | PubMed |
description | The GGAs (Golgi-localized, γ ear–containing, ADP ribosylation factor–binding proteins) are multidomain proteins implicated in protein trafficking between the Golgi and endosomes. We examined whether the three mammalian GGAs act independently or together to mediate their functions. Using cryo-immunogold electron microscopy, the three GGAs were shown to colocalize within coated buds and vesicles at the trans-Golgi network (TGN) of HeLa cells. In vitro binding experiments revealed multidomain interactions between the GGAs, and chemical cross-linking experiments demonstrated that GGAs 1 and 2 form a complex on Golgi membranes. RNA interference of each GGA resulted in decreased levels of the other GGAs and their redistribution from the TGN to cytosol. This was associated with impaired incorporation of the cation-independent mannose 6-phosphate receptor into clathrin-coated vesicles at the TGN, partial redistribution of the receptor to endosomes, and missorting of cathepsin D. The morphology of the TGN was also altered. These findings indicate that the three mammalian GGAs cooperate to sort cargo and are required for maintenance of TGN structure. |
format | Text |
id | pubmed-2173681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21736812008-05-01 Mammalian GGAs act together to sort mannose 6-phosphate receptors Ghosh, Pradipta Griffith, Janice Geuze, Hans J. Kornfeld, Stuart J Cell Biol Article The GGAs (Golgi-localized, γ ear–containing, ADP ribosylation factor–binding proteins) are multidomain proteins implicated in protein trafficking between the Golgi and endosomes. We examined whether the three mammalian GGAs act independently or together to mediate their functions. Using cryo-immunogold electron microscopy, the three GGAs were shown to colocalize within coated buds and vesicles at the trans-Golgi network (TGN) of HeLa cells. In vitro binding experiments revealed multidomain interactions between the GGAs, and chemical cross-linking experiments demonstrated that GGAs 1 and 2 form a complex on Golgi membranes. RNA interference of each GGA resulted in decreased levels of the other GGAs and their redistribution from the TGN to cytosol. This was associated with impaired incorporation of the cation-independent mannose 6-phosphate receptor into clathrin-coated vesicles at the TGN, partial redistribution of the receptor to endosomes, and missorting of cathepsin D. The morphology of the TGN was also altered. These findings indicate that the three mammalian GGAs cooperate to sort cargo and are required for maintenance of TGN structure. The Rockefeller University Press 2003-11-24 /pmc/articles/PMC2173681/ /pubmed/14638859 http://dx.doi.org/10.1083/jcb.200308038 Text en Copyright © 2003, The Rockefeller University Press 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 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Ghosh, Pradipta Griffith, Janice Geuze, Hans J. Kornfeld, Stuart Mammalian GGAs act together to sort mannose 6-phosphate receptors |
title | Mammalian GGAs act together to sort mannose 6-phosphate receptors |
title_full | Mammalian GGAs act together to sort mannose 6-phosphate receptors |
title_fullStr | Mammalian GGAs act together to sort mannose 6-phosphate receptors |
title_full_unstemmed | Mammalian GGAs act together to sort mannose 6-phosphate receptors |
title_short | Mammalian GGAs act together to sort mannose 6-phosphate receptors |
title_sort | mammalian ggas act together to sort mannose 6-phosphate receptors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173681/ https://www.ncbi.nlm.nih.gov/pubmed/14638859 http://dx.doi.org/10.1083/jcb.200308038 |
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