TY - JOUR
T1 - Ankyrin-B regulates Kir6.2 membrane expression and function in heart
AU - Li, Jingdong
AU - Kline, Crystal F.
AU - Hund, Thomas J.
AU - Anderson, Mark E.
AU - Mohler, Peter J.
PY - 2010/9/10
Y1 - 2010/9/10
N2 - Ankyrin polypeptides are critical for normal membrane protein expression in diverse cell types, including neurons, myocytes, epithelia, and erythrocytes. Ankyrin dysfunction results in defects in membrane expression of ankyrin-binding partners (including ion channels, transporters, and cell adhesion molecules), resulting in aberrant cellular function and disease. Here, we identify a new role for ankyrin-B in cardiac cell biology. We demonstrate that cardiac sarcolemmal KATP channels directly associate with ankyrin-B in heart via the KATP channel α-subunit Kir6.2. We demonstrate that primary myocytes lacking ankyrin-B display defects in Kir6.2 protein expression, membrane expression, and function. Moreover, we demonstrate a secondary role for ankyrin-B in regulating KATP channel gating. Finally, we demonstrate that ankyrin-B forms a membrane complex with KATP channels and the cardiac Na/K-ATPase, a second key membrane transporter involved in the cardiac ischemia response. Collectively, our new findings define a new role for cardiac ankyrin polypeptides in regulation of ion channel membrane expression in heart.
AB - Ankyrin polypeptides are critical for normal membrane protein expression in diverse cell types, including neurons, myocytes, epithelia, and erythrocytes. Ankyrin dysfunction results in defects in membrane expression of ankyrin-binding partners (including ion channels, transporters, and cell adhesion molecules), resulting in aberrant cellular function and disease. Here, we identify a new role for ankyrin-B in cardiac cell biology. We demonstrate that cardiac sarcolemmal KATP channels directly associate with ankyrin-B in heart via the KATP channel α-subunit Kir6.2. We demonstrate that primary myocytes lacking ankyrin-B display defects in Kir6.2 protein expression, membrane expression, and function. Moreover, we demonstrate a secondary role for ankyrin-B in regulating KATP channel gating. Finally, we demonstrate that ankyrin-B forms a membrane complex with KATP channels and the cardiac Na/K-ATPase, a second key membrane transporter involved in the cardiac ischemia response. Collectively, our new findings define a new role for cardiac ankyrin polypeptides in regulation of ion channel membrane expression in heart.
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U2 - 10.1074/jbc.M110.147868
DO - 10.1074/jbc.M110.147868
M3 - Article
C2 - 20610380
AN - SCOPUS:77956528473
SN - 0021-9258
VL - 285
SP - 28723
EP - 28730
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 37
ER -