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

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

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume300
Issue number3
DOIs
StatePublished - Mar 2011

Fingerprint

Syntaxin 1
KATP Channels
Inwardly Rectifying Potassium Channel
Insulin
Sulfonylurea Receptors
Glucose
Membrane Fusion
Secretory Pathway
Exocytosis
Insulin-Secreting Cells
Endocytosis
Small Interfering RNA
Blood Proteins
Membrane Proteins
Up-Regulation
Down-Regulation
Cell Membrane

Keywords

  • ATP-sensitive potassium channel
  • Biogenesis
  • Inwardly rectifying potassium channel 6.2
  • Sulfonylurea receptor
  • Trafficking

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

Syntaxin 1A regulates surface expression of β-cell ATP-sensitive potassium channels. / Chen, Pei Chun; Bruederle, Cathrin E.; Gaisano, Herbert Y.; Shyng, Show-Ling.

In: American Journal of Physiology - Cell Physiology, Vol. 300, No. 3, 03.2011.

Research output: Contribution to journalArticle

@article{1c7bf89c4dab455c8a561b5a94e5d314,
title = "Syntaxin 1A regulates surface expression of β-cell ATP-sensitive potassium channels",
abstract = "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.",
keywords = "ATP-sensitive potassium channel, Biogenesis, Inwardly rectifying potassium channel 6.2, Sulfonylurea receptor, Trafficking",
author = "Chen, {Pei Chun} and Bruederle, {Cathrin E.} and Gaisano, {Herbert Y.} and Show-Ling Shyng",
year = "2011",
month = "3",
doi = "10.1152/ajpcell.00429.2010",
language = "English (US)",
volume = "300",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - Syntaxin 1A regulates surface expression of β-cell ATP-sensitive potassium channels

AU - Chen, Pei Chun

AU - Bruederle, Cathrin E.

AU - Gaisano, Herbert Y.

AU - Shyng, Show-Ling

PY - 2011/3

Y1 - 2011/3

N2 - 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.

AB - 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.

KW - ATP-sensitive potassium channel

KW - Biogenesis

KW - Inwardly rectifying potassium channel 6.2

KW - Sulfonylurea receptor

KW - Trafficking

UR - http://www.scopus.com/inward/record.url?scp=79952129862&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952129862&partnerID=8YFLogxK

U2 - 10.1152/ajpcell.00429.2010

DO - 10.1152/ajpcell.00429.2010

M3 - Article

VL - 300

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 3

ER -