title: Golgi-localizing, gamma-adaptin ear homology domain, ADP-ribosylation factor-binding (GGA) proteins interact with acidic dileucine sequences within the cytoplasmic domains of sorting receptors through their Vps27p/Hrs/STAM (VHS) domains.
abstract: GGA (Golgi-localizing, gamma-adaptin ear homology domain, ARF-binding) proteins are potential effectors of ADP-ribosylation factors, are associated with the trans-Golgi network (TGN), and are involved in protein transport from this compartment. By yeast two-hybrid screening and subsequent two-hybrid and pull-down analyses, we have shown that GGA proteins, through their VHS (Vps27p/Hrs/STAM) domains, interact with acidic dileucine sequences found in the cytoplasmic domains of TGN-localized sorting receptors such as sortilin and mannose 6-phosphate receptor. A mutational analysis has revealed that a leucine pair and a cluster of acidic residues adjacent to the pair are mainly responsible for the interaction. A chimeric receptor with the sortilin cytoplasmic domain localizes to the TGN, whereas the chimeric receptor with a mutation at the leucine pair or the acidic cluster is mislocalized to punctate structures reminiscent of early endosomes. These results indicate that GGA proteins regulate the localization to or exit from the TGN of the sorting receptors.
authors.affiliation: Institute of Biological Sciences and Gene Experiment Center, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Katoh
authors.forename: Y
authors.initials: Y
authors.lastname: Shiba
authors.forename: K
authors.initials: K
authors.lastname: Nakayama
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D033982:Adaptor Protein Complex gamma Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000244:Adenosine Diphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D007930:Leucine / Q000737:chemistry*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008562:Membrane Glycoproteins / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017527:Receptor, IGF Type 2 / Q000737:chemistry; D011971:Receptors, Immunologic / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins; D000099183:Sortilin
chemical_list: D020727:ADP-Ribosylation Factors; D033982:Adaptor Protein Complex gamma Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000244:Adenosine Diphosphate; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D018076:DNA, Complementary; D056827:Endosomal Sorting Complexes Required for Transport; D007930:Leucine; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D017527:Receptor, IGF Type 2; D011971:Receptors, Immunologic; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D000099183:Sortilin; C407306:GGA adaptor proteins; C119627:VPS27 protein, S cerevisiae