Sorting of mannose 6-phosphate receptors mediated by the GGAs.
The delivery of soluble hydrolases to lysosomes is mediated by the cation-independent and cation-dependent mannose 6-phosphate receptors. The cytosolic tails of both receptors contain acidic-cluster-dileucine signals that direct sorting from the trans-Golgi network to the endosomal-lysosomal system. We found that these signals bind to the VHS domain of the Golgi-localized, gamma-ear-containing, ARF-binding proteins (GGAs). The receptors and the GGAs left the trans-Golgi network on the same tubulo-vesicular carriers. A dominant-negative GGA mutant blocked exit of the receptors from the trans-Golgi network. Thus, the GGAs appear to mediate sorting of the mannose 6-phosphate receptors at the trans-Golgi network.
Puertollano
R
R
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Aguilar
R C
RC
Gorshkova
I
I
Crouch
R J
RJ
Bonifacino
J S
JS
D020727:ADP-Ribosylation Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002412:Cations; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism; D004151:Dipeptides / Q000737:chemistry / Q000378:metabolism; D004285:Dogs; D006801:Humans; D008856:Microscopy, Fluorescence; 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*; D017527:Receptor, IGF Type 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D022161:Transport Vesicles / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D015003:Yeasts; D021601:trans-Golgi Network / Q000378:metabolism*
D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D002412:Cations; D002966:Clathrin; D004151:Dipeptides; C407306:GGA adaptor proteins; C405944:GGA2 protein, human; D021382:Protein Sorting Signals; D011506:Proteins; D017527:Receptor, IGF Type 2; D011993:Recombinant Fusion Proteins; C038361:leucylleucine; D020727:ADP-Ribosylation Factors