TY - JOUR
T1 - Identification of yeast proteins necessary for cell-surface function of a potassium channel
AU - Haass, Friederike A.
AU - Jonikas, Martin
AU - Walter, Peter
AU - Weissman, Jonathan S.
AU - Jan, Yuh Nung
AU - Jan, Lily Y.
AU - Schuldiner, Maya
PY - 2007/11/13
Y1 - 2007/11/13
N2 - Inwardly rectifying potassium (Kir) channels form gates in the cell membrane that regulate the flow of K+ ions into and out of the cell, thereby influencing the membrane potential and electrical signaling of many cell types, including neurons and cardiomyocytes. Kir-channel function depends on other cellular proteins that aid in the folding of channel subunits, assembly into tetrameric complexes, trafficking of quality-controlled channels to the plasma membrane, and regulation of channel activity at the cell surface. We used the yeast Saccharomyces cerevisiae as a model system to identify proteins necessary for the functional expression of a mammalian Kir channel at the cell surface. A screen of 376 yeast strains, each lacking one nonessential protein localized to the early secretory pathway, identified seven deletion strains in which functional expression of the Kir channel at the plasma membrane was impaired. Six deletions were of genes with known functions in trafficking and lipid biosynthesis (sur4Δ, csg2Δ, erv14Δ, emp24Δ, erv25Δ, and bst1Δ), and one deletion was of an uncharacterized gene (yil039wΔ). We provide genetic and functional evidence that Yil039wp, a conserved, phosphoesterase domain-containing protein, which we named "trafficking of Emp24p/Erv25p-dependent cargo disrupted 1" (Ted1p), acts together with Emp24p/Erv25p in cargo exit from the endoplasmic reticulum (ER). The seven yeast proteins identified in our screen likely impact Kir-channel functional expression at the level of vesicle budding from the ER and/or the local lipid environment at the plasma membrane.
AB - Inwardly rectifying potassium (Kir) channels form gates in the cell membrane that regulate the flow of K+ ions into and out of the cell, thereby influencing the membrane potential and electrical signaling of many cell types, including neurons and cardiomyocytes. Kir-channel function depends on other cellular proteins that aid in the folding of channel subunits, assembly into tetrameric complexes, trafficking of quality-controlled channels to the plasma membrane, and regulation of channel activity at the cell surface. We used the yeast Saccharomyces cerevisiae as a model system to identify proteins necessary for the functional expression of a mammalian Kir channel at the cell surface. A screen of 376 yeast strains, each lacking one nonessential protein localized to the early secretory pathway, identified seven deletion strains in which functional expression of the Kir channel at the plasma membrane was impaired. Six deletions were of genes with known functions in trafficking and lipid biosynthesis (sur4Δ, csg2Δ, erv14Δ, emp24Δ, erv25Δ, and bst1Δ), and one deletion was of an uncharacterized gene (yil039wΔ). We provide genetic and functional evidence that Yil039wp, a conserved, phosphoesterase domain-containing protein, which we named "trafficking of Emp24p/Erv25p-dependent cargo disrupted 1" (Ted1p), acts together with Emp24p/Erv25p in cargo exit from the endoplasmic reticulum (ER). The seven yeast proteins identified in our screen likely impact Kir-channel functional expression at the level of vesicle budding from the ER and/or the local lipid environment at the plasma membrane.
KW - Epistasis mini array profile
KW - GIRK2
KW - GPI anchor
KW - YIL039W/TED1
KW - Yeast deletion library
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U2 - 10.1073/pnas.0708765104
DO - 10.1073/pnas.0708765104
M3 - Article
C2 - 17989219
AN - SCOPUS:36749064494
SN - 0027-8424
VL - 104
SP - 18079
EP - 18084
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 46
ER -