SGD Paper 
De M, et al. (2012) Direct Binding of the Kex2p Cytosolic Tail to the VHS Domain of Yeast Gga2p Facilitates TGN to Prevacuolar Compartment Transport and is Regulated by Phosphorylation. Mol Biol Cell ()
Abstract: Human GGAs bind directly to acidic dileucine sorting motifs in the cytosolic tails (C-tails) of intracellular receptors. Despite evidence for a role in recruiting ubiquitinated cargo, it remains unclear whether yeast Ggas also function by binding peptide sorting signals directly. Two-hybrid analysis shows that the Gga1p and Gga2p VHS domains both bind a site in the Kex2p C-tail and that the Gga2p VHS domain binds a site in the Vps10p C-tail. Binding requires deletion of an apparently auto-inhibitory sequence in the Gga2p hinge. Ser(780) in the Kex2p C-tail is crucial for binding: an Ala substitution blocks but an Asp substitution permits binding. Biochemical assays using purified Gga2p VHS-GAT and GST-Kex2p C-tail fusions show that Gga2p binds directly to the Kex2p C-tail, with relative affinities: Asp(780)>Ser(780)>Ala(780). Affinity-purified antibody against a peptide containing phospho-Ser-(780) recognizes WT Kex2p but not S(780)A Kex2p, showing that Ser(780) is phosphorylated in vivo; phosphorylation of Ser(780) is up-regulated by cell-wall damaging drugs. Finally, mutation of Ser(780) alters trafficking of Kex2p both in vivo and in cell-free TGN-PVC transport. Thus, yeast Gga adaptors facilitate TGN-PVC transport by direct binding of non-canonical phosphoregulated Gga-binding sites in cargo molecules.
| Status: Epub ahead of print | Type: Journal Article | PubMed ID: 23264466 |
Topics addressed in this paper
Number of different genes curated to this paper: 4
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