Binding of GGA2 to the lysosomal enzyme sorting motif of the mannose 6-phosphate receptor.
The GGAs are a multidomain protein family implicated in protein trafficking between the Golgi and endosomes. Here, the VHS domain of GGA2 was shown to bind to the acidic cluster-dileucine motif in the cytoplasmic tail of the cation-independent mannose 6-phosphate receptor (CI-MPR). Receptors with mutations in this motif were defective in lysosomal enzyme sorting. The hinge domain of GGA2 bound clathrin, suggesting that GGA2 could be a link between cargo molecules and clathrin-coated vesicle assembly. Thus, GGA2 binding to the CI-MPR is important for lysosomal enzyme targeting.
Zhu
Y
Y
Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Doray
B
B
Poussu
A
A
Lehto
V P
VP
Kornfeld
S
S
D033942:Adaptor Proteins, Vesicular Transport; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D002412:Cations; D002966:Clathrin / Q000378:metabolism; D004151:Dipeptides / Q000737:chemistry / Q000378:metabolism; D007739:L Cells; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017527:Receptor, IGF Type 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D018808:Transcription Factor AP-1 / Q000378:metabolism; D022161:Transport Vesicles / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D021601:trans-Golgi Network / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D002412:Cations; D002966:Clathrin; D004151:Dipeptides; C405944:GGA2 protein, human; D021382:Protein Sorting Signals; D011506:Proteins; D017527:Receptor, IGF Type 2; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; C038361:leucylleucine