Open AccessESCRT regulates surface expression of the Kir2.1 potassium channel
Author(s) -
Alexander Kolb,
Patrick G. Needham,
Cari Rothenberg,
Christopher J. Guerriero,
Paul A. Welling,
Jeffrey L. Brodsky
Publication year - 2014
Publication title -
molecular biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.463
H-Index - 225
eISSN - 1939-4586
pISSN - 1059-1524
DOI - 10.1091/mbc.e13-07-0394
Subject(s) - escrt , biology , endoplasmic reticulum associated protein degradation , microbiology and biotechnology , endoplasmic reticulum , endosome , potassium channel , ion channel , protein degradation , transport protein , biochemistry , unfolded protein response , intracellular , biophysics , receptor
Protein quality control (PQC) is required to ensure cellular health. PQC is recognized for targeting the destruction of defective polypeptides, whereas regulated protein degradation mechanisms modulate the concentration of specific proteins in concert with physiological demands. For example, ion channel levels are physiologically regulated within tight limits, but a system-wide approach to define which degradative systems are involved is lacking. We focus on the Kir2.1 potassium channel because altered Kir2.1 levels lead to human disease and Kir2.1 restores growth on low-potassium medium in yeast mutated for endogenous potassium channels. Using this system, first we find that Kir2.1 is targeted for endoplasmic reticulum–associated degradation (ERAD). Next a synthetic gene array identifies nonessential genes that negatively regulate Kir2.1. The most prominent gene family that emerges from this effort encodes members of endosomal sorting complex required for transport (ESCRT). ERAD and ESCRT also mediate Kir2.1 degradation in human cells, with ESCRT playing a more prominent role. Thus multiple proteolytic pathways control Kir2.1 levels at the plasma membrane.