Syntaxin 1A regulates surface expression of beta-cell ATP-sensitive potassium channels.
نویسندگان
چکیده
The pancreatic ATP-sensitive potassium (K(ATP)) 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 K(ATP) 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 K(ATP) 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 K(ATP) 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 K(ATP) 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 K(ATP) channel gating, Syn-1A also regulates K(ATP) 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 K(ATP) channel expression.
منابع مشابه
Syntaxin 1 A regulates surface expression of β - cell ATP - sensitive 1 potassium channels
26 The pancreatic ATP-sensitive potassium (KATP) channel consisting of four Kir6.2 and 27 four sulfonylurea receptor SUR1 subunits play a key role in insulin secretion by 28 linking glucose metabolism to membrane excitability. Syntaxin 1A is a plasma 29 membrane protein important for membrane fusion during exocytosis of insulin 30 granules. Here, we show that syntaxin 1A and KATP channels endog...
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ورودعنوان ژورنال:
- American journal of physiology. Cell physiology
دوره 300 3 شماره
صفحات -
تاریخ انتشار 2011