Identification of yeast proteins necessary for cell-surface function of a potassium channel

Friederike A. Haass, Martin Jonikas, Peter Walter, Jonathan S. Weissman, Yuh Nung Jan, Lily Y. Jan, Maya Schuldiner

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)18079-18084
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number46
DOIs
StatePublished - Nov 13 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Epistasis mini array profile
  • GIRK2
  • GPI anchor
  • YIL039W/TED1
  • Yeast deletion library

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