title: Two novel WD40 domain-containing proteins, Ere1 and Ere2, function in the retromer-mediated endosomal recycling pathway.
abstract: Regulated secretion, nutrient uptake, and responses to extracellular signals depend on cell-surface proteins that are internalized and recycled back to the plasma membrane. However, the underlying mechanisms that govern membrane protein recycling to the cell surface are not fully known. Using a chemical-genetic screen in yeast, we show that the arginine transporter Can1 is recycled back to the cell surface via two independent pathways mediated by the sorting nexins Snx4/41/42 and the retromer complex, respectively. In addition, we identify two novel WD40-domain endosomal recycling proteins, Ere1 and Ere2, that function in the retromer pathway. Ere1 is required for Can1 recycling via the retromer-mediated pathway, but it is not required for the transport of other retromer cargoes, such as Vps10 and Ftr1. Biochemical studies reveal that Ere1 physically interacts with internalized Can1. Ere2 is present in a complex containing Ere1 on endosomes and functions as a regulator of Ere1. Taken together, our results suggest that Snx4/41/42 and the retromer comprise two independent pathways for the recycling of internalized cell-surface proteins. Moreover, a complex containing the two novel proteins Ere1 and Ere2 mediates cargo-specific recognition by the retromer pathway.
authors: Weill Institute for Cell and Molecular Biology and Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
authors: Yufeng
authors: Y
authors: Shi
authors: Christopher J
authors: CJ
authors: Stefan
authors: Sarah M
authors: SM
authors: Rue
authors: David
authors: D
authors: Teis
authors: Scott D
authors: SD
authors: Emr
mesh_terms: D026923:Amino Acid Transport Systems, Basic / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D055786:Gene Knockout Techniques; D015723:Gene Library; D008856:Microscopy, Fluorescence; D046912:Multiprotein Complexes / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D058305:Sorting Nexins / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D012359:tRNA Methyltransferases
chemical_list: D026923:Amino Acid Transport Systems, Basic; C502212:CAN1 protein, S cerevisiae; D056827:Endosomal Sorting Complexes Required for Transport; D046912:Multiprotein Complexes; C570231:RRT2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D058305:Sorting Nexins; C106932:VPS5 protein, S cerevisiae; D033921:Vesicular Transport Proteins; C570232:RTT10 protein, S cerevisiae; D012359:tRNA Methyltransferases