PMID:17344478

Citation	Kim, Y, Deng, Y and Philpott, CC (2007) GGA2- and ubiquitin-dependent trafficking of Arn1, the ferrichrome transporter of Saccharomyces cerevisiae. Mol. Biol. Cell 18:1790-802
Abstract	The intracellular trafficking of Arn1, a ferrichrome transporter in Saccharomyces cerevisiae, is controlled in part by the binding of ferrichrome to the transporter. In the absence of ferrichrome, Arn1 is sorted directly from the Golgi to endosomes. Ferrichrome binding triggers the redistribution of Arn1 to the plasma membrane, whereas ferrichrome transport is associated with the cycling of Arn1 between the plasma membrane and endosomes. Here, we report that the clathrin adaptor Gga2 and ubiquitination by the Rsp5 ubiquitin ligase are required for trafficking of Arn1. Gga2 was required for Golgi-to-endosomal trafficking of Arn1, which was sorted from endosomes to the vacuole for degradation. Trafficking into the vacuolar lumen was dependent on ubiquitination by Rsp5, but ubiquitination was not required for plasma membrane accumulation of Arn1 in the presence of ferrichrome. Retrograde trafficking via the retromer complex or Snx4 was also not required for plasma membrane accumulation. High concentrations of ferrichrome led to higher levels of ubiquitination of Arn1, but they did not induce degradation. Without this ubiquitination, Arn1 remained on the plasma membrane, where it was active for transport. Arn1 was preferentially modified with polyubiquitin chains on a cluster of lysine residues at the amino terminus of the transporter.
Links	PubMed PMC1855028 Online version:10.1091/mbc.E06-09-0861
Keywords	Adaptor Proteins, Vesicular Transport/genetics; Adaptor Proteins, Vesicular Transport/metabolism; Amino Acid Sequence; Amino Acid Substitution; Base Sequence; Biological Transport, Active; Cell Membrane/metabolism; DNA, Fungal/genetics; Endocytosis; Endosomal Sorting Complexes Required for Transport; Ferrichrome/metabolism; Genes, Fungal; Golgi Apparatus/metabolism; Lysine/chemistry; Membrane Transport Proteins/chemistry; Membrane Transport Proteins/genetics; Membrane Transport Proteins/metabolism; Molecular Sequence Data; Recombinant Proteins/chemistry; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/chemistry; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Ubiquitin/metabolism; Ubiquitin-Protein Ligase Complexes/genetics; Ubiquitin-Protein Ligase Complexes/metabolism; Vacuoles/metabolism
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