ABCMdb

PMID: 15987767

Yan FF, Lin CW, Cartier EA, Shyng SL
Role of ubiquitin-proteasome degradation pathway in biogenesis efficiency of {beta}-cell ATP-sensitive potassium channels.
Am J Physiol Cell Physiol. 2005 Nov;289(5):C1351-9. Epub 2005 Jun 29., [PubMed]

Sentences

No. Mutations Sentence Comment

228 ABCC8 p.Val187Asp ABCC8 p.Ala116Pro Three SUR1 mutations, A116P, V187D, and ⌬F1388, which we have previously shown to result in ER retention and surface expression defects of KATP channels, were tested. Login to comment 229 ABCC8 p.Val187Asp ABCC8 p.Ala116Pro Three SUR1 mutations, A116P, V187D, and èc;F1388, which we have previously shown to result in ER retention and surface expression defects of KATP channels, were tested. Login to comment 231 ABCC8 p.Val187Asp ABCC8 p.Ala116Pro To further test this hypothesis, we examined the combined effect of glibenclamide and MG132 on surface expression of the A116P and V187D mutants. Login to comment 232 ABCC8 p.Val187Asp ABCC8 p.Val187Asp ABCC8 p.Ala116Pro ABCC8 p.Ala116Pro Sulfonylureas such as glibenclamide have previously been shown to significantly increase surface expression of the A116P and V187D mutants, presumably by acting as pharmacological chaperones to help mutant SUR1 fold more efficiently (42). Login to comment 233 ABCC8 p.Val187Asp ABCC8 p.Val187Asp ABCC8 p.Ala116Pro ABCC8 p.Ala116Pro We found that pretreatment of COS cells expressing the A116P or the V187D mutant with 5 ␮M glibenclamide led to a significant increase in mutant channel surface expression (P Ͻ 0.01) on subsequent exposure to the proteasome inhibitor MG132 (Fig. 7B). Login to comment 234 ABCC8 p.Val187Asp ABCC8 p.Ala116Pro We found that pretreatment of COS cells expressing the A116P or the V187D mutant with 5 òe;M glibenclamide led to a significant increase in mutant channel surface expression (P b0d; 0.01) on subsequent exposure to the proteasome inhibitor MG132 (Fig. 7B). Login to comment 245 ABCC8 p.Val187Asp ABCC8 p.Ala116Pro A: COSm6 cells transiently coexpressing Kir6.2 and wild-type (WT) fSUR1 or fSUR1 bearing the A116P, V187D, or ⌬F1388 mutation were treated with or without 10 ␮M MG132 for 6 h and processed for chemiluminescence assays to quantify channel expression level at the cell surface. Login to comment 246 ABCC8 p.Val187Asp ABCC8 p.Ala116Pro A: COSm6 cells transiently coexpressing Kir6.2 and wild-type (WT) fSUR1 or fSUR1 bearing the A116P, V187D, or èc;F1388 mutation were treated with or without 10 òe;M MG132 for 6 h and processed for chemiluminescence assays to quantify channel expression level at the cell surface. Login to comment 248 ABCC8 p.Val187Asp ABCC8 p.Ala116Pro B: cells expressing Kir6.2 and WT-, A116P-, or V187D-fSUR1 were treated for 24 h with (Glib) or without (Control) 5 ␮M glibenclamide. Login to comment 249 ABCC8 p.Val187Asp ABCC8 p.Ala116Pro B: cells expressing Kir6.2 and WT-, A116P-, or V187D-fSUR1 were treated for 24 h with (Glib) or without (Control) 5 òe;M glibenclamide. Login to comment 260 ABCC8 p.Val187Asp ABCC8 p.Ala116Pro Among them, ⌬F1388 has been proposed to cause severe folding defects, whereas A116P and V187D appear to have milder defects that can be partially overcome by sulfonylurea treatment. Login to comment 262 ABCC8 p.Val187Asp ABCC8 p.Val187Asp ABCC8 p.Ala116Pro ABCC8 p.Ala116Pro However, after pretreatment with glibenclamide, the A116P and V187D mutant channels responded to proteasome inhibitors with a statistically significant increase in surface expression (Fig. 7B). Login to comment 264 ABCC8 p.Val187Asp ABCC8 p.Ala116Pro However, after pretreatment with glibenclamide, the A116P and V187D mutant channels responded to proteasome inhibitors with a statistically significant increase in surface expression (Fig. 7B). Login to comment