Select α-arrestins control cell-surface abundance of the mammalian Kir2.1 potassium channel in a yeast model.

Autor:	Hager NA; From the Department of Biological Sciences, Duquesne University, Pittsburgh, Pennsylvania 15282., Krasowski CJ; From the Department of Biological Sciences, Duquesne University, Pittsburgh, Pennsylvania 15282., Mackie TD; the Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260., Kolb AR; the Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260., Needham PG; the Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260., Augustine AA; the Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260., Dempsey A; the Molecular Biosensor and Imaging Center, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213., Szent-Gyorgyi C; the Molecular Biosensor and Imaging Center, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213., Bruchez MP; the Molecular Biosensor and Imaging Center, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213., Bain DJ; the Department of Geology and Environmental Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, and., Kwiatkowski AV; the Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261., O'Donnell AF; From the Department of Biological Sciences, Duquesne University, Pittsburgh, Pennsylvania 15282, odonne15@duq.edu., Brodsky JL; the Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, jbrodsky@pitt.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2018 Jul 13; Vol. 293 (28), pp. 11006-11021. Date of Electronic Publication: 2018 May 21.
DOI:	10.1074/jbc.RA117.001293
Abstrakt:	Protein composition at the plasma membrane is tightly regulated, with rapid protein internalization and selective targeting to the cell surface occurring in response to environmental changes. For example, ion channels are dynamically relocalized to or from the plasma membrane in response to physiological alterations, allowing cells and organisms to maintain osmotic and salt homeostasis. To identify additional factors that regulate the selective trafficking of a specific ion channel, we used a yeast model for a mammalian potassium channel, the K + inward rectifying channel Kir2.1. Kir2.1 maintains potassium homeostasis in heart muscle cells, and Kir2.1 defects lead to human disease. By examining the ability of Kir2.1 to rescue the growth of yeast cells lacking endogenous potassium channels, we discovered that specific α-arrestins regulate Kir2.1 localization. Specifically, we found that the Ldb19/Art1, Aly1/Art6, and Aly2/Art3 α-arrestin adaptor proteins promote Kir2.1 trafficking to the cell surface, increase Kir2.1 activity at the plasma membrane, and raise intracellular potassium levels. To better quantify the intracellular and cell-surface populations of Kir2.1, we created fluorogen-activating protein fusions and for the first time used this technique to measure the cell-surface residency of a plasma membrane protein in yeast. Our experiments revealed that two α-arrestin effectors also control Kir2.1 localization. In particular, both the Rsp5 ubiquitin ligase and the protein phosphatase calcineurin facilitated the α-arrestin-mediated trafficking of Kir2.1. Together, our findings implicate α-arrestins in regulating an additional class of plasma membrane proteins and establish a new tool for dissecting the trafficking itinerary of any membrane protein in yeast. (© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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