Unknown

Dataset Information

0

Dual role of K ATP channel C-terminal motif in membrane targeting and metabolic regulation.


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.

SUBMITTER: Kline CF 

PROVIDER: S-EPMC2757796 | biostudies-other | 2009 Sep

REPOSITORIES: biostudies-other

altmetric image

Publications

Dual role of K ATP channel C-terminal motif in membrane targeting and metabolic regulation.

Kline Crystal F CF   Kurata Harley T HT   Hund Thomas J TJ   Cunha Shane R SR   Koval Olha M OM   Wright Patrick J PJ   Christensen Matthew M   Anderson Mark E ME   Nichols Colin G CG   Mohler Peter J PJ  

Proceedings of the National Academy of Sciences of the United States of America 20090915 39


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.  ...[more]

Similar Datasets

| S-EPMC8698299 | biostudies-literature
| S-EPMC3419011 | biostudies-literature
| S-EPMC2867903 | biostudies-literature
| S-EPMC3141999 | biostudies-literature
| S-EPMC4858208 | biostudies-literature
| S-EPMC9312261 | biostudies-literature
| S-EPMC3242775 | biostudies-literature
| S-EPMC8810396 | biostudies-literature
| S-EPMC4036241 | biostudies-literature
| S-EPMC3109179 | biostudies-literature