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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...

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Detalles Bibliográficos
Autores principales: Ghosh, Pradipta, Griffith, Janice, Geuze, Hans J., Kornfeld, Stuart
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
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.
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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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