Journal article
Dual role of K-ATP channel C-terminal motif in membrane targeting and metabolic regulation
Proceedings of the National Academy of Sciences - PNAS, Vol.106(39), pp.16669-16674
09/29/2009
DOI: 10.1073/pnas.0907138106
PMCID: PMC2757796
PMID: 19805355
Abstract
The coordinated sorting of ion channels to specific plasma membrane domains is necessary for excitable cell physiology. K-ATP channels, assembled from pore-forming (Kir6.x) and regulatory sulfonylurea receptor subunits, are critical electrical transducers of the metabolic state of excitable tissues, including skeletal and smooth muscle, heart, brain, kidney, and pancreas. Here we show that the C-terminal domain of Kir6.2 contains a motif conferring membrane targeting in primary excitable cells. Kir6.2 lacking this motif displays aberrant channel targeting due to loss of association with the membrane adapter ankyrin-B (AnkB). Moreover, we demonstrate that this Kir6.2 C-terminal AnkB-binding motif (ABM) serves a dual role in K-ATP channel trafficking and membrane metabolic regulation and dysfunction in these pathways results in human excitable cell disease. Thus, the K-ATP channel ABM serves as a previously unrecognized bifunctional touch-point for grading K-ATP channel gating and membrane targeting and may play a fundamental role in controlling excitable cell metabolic regulation.
Details
- Title: Subtitle
- Dual role of K-ATP channel C-terminal motif in membrane targeting and metabolic regulation
- Creators
- Crystal F. Kline - University of IowaHarley T. Kurata - University of IowaThomas J. Hund - University of IowaShane R. Cunha - University of IowaOlha M. Koval - University of IowaPatrick J. Wright - University of IowaMatthew Christensen - University of IowaMark E. Anderson - University of IowaColin G. Nichols - Washington University in St. LouisPeter J. Mohler - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.106(39), pp.16669-16674
- Publisher
- Natl Acad Sciences
- DOI
- 10.1073/pnas.0907138106
- PMID
- 19805355
- PMCID
- PMC2757796
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Number of pages
- 6
- Grant note
- 1-08-RA-141 / American Diabetes Association (ADA); American Diabetes Association HL084583; HL083422; HL079031; HL62494; HL70250; HL95010; HL53268; HL092232 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA PewScholars Trust 0930378N / American Heart Association (AHA); American Heart Association R01HL096652 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 09/29/2009
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984359955302771
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