GGA proteins bind ubiquitin to facilitate sorting at the trans-Golgi network

Patricia M Scott, Patricia S. Bilodeau, Olga Zhdankina, Stanley C. Winistorfer, Melissa J. Hauglund, Margaret M. Allaman, William R. Kearney, Andrew D. Robertson, Annette L. Boman, Robert C. Piper

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133 Scopus citations


Ubiquitination functions as a sorting signal for lysosomal degradation of cell-surface proteins by facilitating their internalization from the plasma membrane and incorporation into lumenal vesicles of multivesicular bodies (MVBs). Ubiquitin may also mediate sorting of proteins from the trans-Golgi network (TGN) to the endosome, thereby preventing their appearance on the cell surface and hastening their degradation in the lysosome-vacuole. Substantiation of a direct ubiquitin-dependent TGN sorting pathway relies in part on identifying candidate machinery that may function as a ubiquitin-sorting 'receptor'at the TGN. Members of the GGA family of coat proteins localize to the TGN and promote the incorporation of proteins into clathrin-coated vesicles destined for transport to endosomes. We show that the GGA coat proteins bind directly to ubiquitin through their GAT domain and demonstrate that this interaction is required for the ubiquitin-dependent sorting of the Gap1 amino acid transporter from the TGN to endosomes. Thus, GGA proteins fulfill the role of ubiquitin sorting receptors at the TGN.

Original languageEnglish (US)
Pages (from-to)252-259
Number of pages8
JournalNature Cell Biology
Issue number3
StatePublished - Mar 2004

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grant GM58202 (R.C.P.), NIH grant GM46869 (A.D.R.) and an American Cancer Society grant RSG-03-020-01-CSM (A.L.B. and P.M.S). W.R.K. and M.M.A. were supported by the University of Iowa College of Medicine. We would like to thank S. Rensink for help with the two-hybrid analysis and D. Connor with strain construction. This work is dedicated to the memory of Annette Lorraine Boman who died in March 2003. We remain inspired by her insight, propelled by her enthusiasm, and encouraged by her love of life and science.


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