Syntaxin 1A regulates surface expression of β-cell ATP-sensitive potassium channels

Pei Chun Chen, Cathrin E. Bruederle, Herbert Y. Gaisano, Show Ling Shyng

研究成果: Article同行評審

26 引文 斯高帕斯(Scopus)

摘要

The pancreatic ATP-sensitive potassium (KATP) channel consisting of four inwardly rectifying potassium channel 6.2 (Kir6.2) and four sulfonylurea receptor SUR1 subunits plays a key role in insulin secretion by linking glucose metabolism to membrane excitability. Syntaxin 1A (Syn-1A) is a plasma membrane protein important for membrane fusion during exocytosis of insulin granules. Here, we show that Syn-1A and KATP channels endogenously expressed in the insulin-secreting cell INS-1 interact. Upregulation of Syn-1A by overexpression in INS-1 leads to a decrease, whereas downregulation of Syn-1A by small interfering RNA (siRNA) leads to an increase, in surface expression of KATP channels. Using COSm6 cells as a heterologous expression system for mechanistic investigation, we found that Syn-1A interacts with SUR1 but not Kir6.2. Furthermore, Syn-1A decreases surface expression of KATP channels via two mechanisms. One mechanism involves accelerated endocytosis of surface channels. The other involves decreased biogenesis and processing of channels in the early secretory pathway. This regulation is KATP channel specific as Syn-1A has no effect on another inward rectifier potassium channel Kir3.1/3.4. Our results demonstrate that in addition to a previously documented role in modulating KATP channel gating, Syn-1A also regulates KATP channel expression in β-cells. We propose that physiological or pathological changes in Syn-1A expression may modulate insulin secretion by altering glucose-secretion coupling via changes in KATP channel expression.

原文English
頁(從 - 到)C506-C516
期刊American Journal of Physiology - Cell Physiology
300
發行號3
DOIs
出版狀態Published - 2011 3月

All Science Journal Classification (ASJC) codes

  • 生理學
  • 細胞生物學

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