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| Interactions of GGA3 with the ubiquitin sorting machinery |
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| Author(s): Puertollano R, Bonifacino JS |
| Source: NATURE CELL BIOLOGY Volume: 6 Issue: 3 Pages: 244-251 Published: MAR 2004 |
| Times Cited: 99 References: 34 |
| Abstract: The Golgi-localized, gamma-ear-containing, Arf-binding (GGA) proteins constitute a family of clathrin adaptors that are mainly associated with the trans-Golgi network (TGN)(1-3) and mediate the sorting of mannose 6-phosphate receptors(4-6). This sorting is dependent on the interaction of the VHS domain of the GGAs with acidic-cluster-dileucine signals in the cytosolic tails of the receptors(4,5). Here we demonstrate the existence of another population of GGAs that are associated with early endosomes. RNA interference (RNAi) of GGA3 expression results in accumulation of the cation-independent mannose 6-phosphate receptor and internalized epidermal growth factor (EGF) within enlarged early endosomes. This perturbation impairs the degradation of internalized EGF, a process that is normally dependent on the sorting of ubiquitinated EGF receptors (EGFRs) to late endosomes. Protein interaction analyses show that the GGAs bind ubiquitin. The VHS and GAT domains of GGA3 are responsible for this binding, as well as for interactions with TSG101, a component of the ubiquitin-dependent sorting machinery. Thus, GGAs may have additional roles in sorting of ubiquitinated cargo. |
| Document Type: Article |
| Language: English |
| Reprint Address: Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA |
Addresses:
1. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Cell Biology |
| IDS Number: 780GB |
| ISSN: 1465-7392 |
| DOI: 10.1038/ncb1106 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |