Role of ubiquitin-proteasome degradation pathway in biogenesis efficiency of β-cell ATP-sensitive potassium channels

Fei Fei Yan, Chia Wei Lin, Etienne A. Cartier, Show-Ling Shyng

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

ATP-sensitive potassium (KATP) channels of pancreatic β-cells mediate glucose-induced insulin secretion by linking glucose metabolism to membrane excitability. The number of plasma membrane K ATP channels determines the sensitivity of β-cells to glucose stimulation. The KATP channel is formed in the endoplasmic reticulum (ER) on coassembly of four inwardly rectifying potassium channel Kir6.2 subunits and four sulfonylurea receptor 1 (SUR1) subunits. Little is known about the cellular events that govern the channel's biogenesis efficiency and expression. Recent studies have implicated the ubiquitin-proteasome pathway in modulating surface expression of several ion channels. In this work, we investigated whether the ubiquitin-proteasome pathway plays a role in the biogenesis efficiency and surface expression of KATP channels. We provide evidence that, when expressed in COS cells, both Kir6.2 and SUR1 undergo ER-associated degradation via the ubiquitin-proteasome system. Moreover, treatment of cells with proteasome inhibitors MG132 or lactacystin leads to increased surface expression of KATP channels by increasing the efficiency of channel biogenesis. Importantly, inhibition of proteasome function in a pancreatic β-cell line, INS-1, that express endogenous K ATP channels also results in increased channel number at the cell surface, as assessed by surface biotinylation and whole cell patch-clamp recordings. Our results support a role of the ubiquitin-proteasome pathway in the biogenesis efficiency and surface expression of β-cell KATP channels.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume289
Issue number5 58-5
DOIs
StatePublished - Nov 2005

Fingerprint

KATP Channels
Proteasome Endopeptidase Complex
Ubiquitin
Degradation
Sulfonylurea Receptors
Adenosine Triphosphate
Glucose
Endoplasmic Reticulum-Associated Degradation
Cells
Inwardly Rectifying Potassium Channel
Biotinylation
Proteasome Inhibitors
COS Cells
Clamping devices
Cell membranes
Ion Channels
Metabolism
Endoplasmic Reticulum
Potassium
Cell Count

Keywords

  • Endoplasmic reticulum-associated degradation
  • Kir6.2
  • Proteasome inhibitors
  • Sulfonylurea receptor-1

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Role of ubiquitin-proteasome degradation pathway in biogenesis efficiency of β-cell ATP-sensitive potassium channels. / Yan, Fei Fei; Lin, Chia Wei; Cartier, Etienne A.; Shyng, Show-Ling.

In: American Journal of Physiology - Cell Physiology, Vol. 289, No. 5 58-5, 11.2005.

Research output: Contribution to journalArticle

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