GGA proteins bind ubiquitin to facilitate sorting at the trans-Golgi network.
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.
Scott
Patricia M
PM
Department of Biochemistry and Molecular Biology, University of Minnesota School of Medicine Duluth, Duluth, MN 55812, USA. pscott@d.umn.edu
Bilodeau
Patricia S
PS
Zhdankina
Olga
O
Winistorfer
Stanley C
SC
Hauglund
Melissa J
MJ
Allaman
Margaret M
MM
Kearney
William R
WR
Robertson
Andrew D
AD
Boman
Annette L
AL
Piper
Robert C
RC
D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport; D026905:Amino Acid Transport Systems / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D022161:Transport Vesicles / Q000502:physiology; D021601:trans-Golgi Network / Q000378:metabolism*
D033942:Adaptor Proteins, Vesicular Transport; D026905:Amino Acid Transport Systems; D002352:Carrier Proteins; C407306:GGA adaptor proteins; C405944:GGA2 protein, human; D020727:ADP-Ribosylation Factors