期刊
CELL COMMUNICATION AND ADHESION
卷 18, 期 4, 页码 57-65出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/15419061.2011.611920
关键词
Connexin43; gap junctions; cardiomyocytes; G alpha q; alpha-adrenergic; norepinephrine; ubiquitination; internalization
资金
- Danish National Research Foundation
- Danish Cardiovascular Research Academy
- Danish Natural and Health Sciences Research Councils
G alpha(q)-stimulation reduces intercellular coupling within 10 min via a decrease in the membrane lipid phosphatidylinositol-4,5-bisphosphate (PIP2), but the mechanism is unknown. Here we show that uncoupling in rat cardiomyocytes after stimulation of alpha-adrenergic G alpha(q)-coupled receptors with norepinephrine is prevented by proteasomal and lysosomal inhibitors, suggesting that internalization and possibly degradation of connexin43 (Cx43) is involved. Uncoupling was accompanied by increased Triton X-100 solubility of Cx43, which is considered a measure of the non-junctional pool of Cx43. However, inhibition of the proteasome and lysosome further increased solubility while preserving coupling, suggesting that communicating gap junctions can be part of the soluble fraction. Ubiquitination of Cx43 was also increased, and Cx43 co-immunoprecipitated with the ubiquitin ligase Nedd4. Conclusions : Norepinephrine increases ubiquitination of Cx43 in cardiomyocytes, possibly via Nedd4. We suggest that Cx43 is subsequently internalized, which is preceded by acquired solubility in Triton X-100, which does not lead to uncoupling per se.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据