ABCMdb

PMID: 20427569

Yan FF, Pratt EB, Chen PC, Wang F, Skach WR, David LL, Shyng SL
Role of Hsp90 in biogenesis of the beta-cell ATP-sensitive potassium channel complex.
Mol Biol Cell. 2010 Jun 15;21(12):1945-54. Epub 2010 Apr 28., [PubMed]

Sentences

No. Mutations Sentence Comment

177 ABCC8 p.Asp310Asn ABCC8 p.Ala116Pro ABCC8 p.Asn24Lys The five mutants examined harbor mutation N24K, A116P, D310N, ⌬F1388, or D1472N in the SUR1 subunit. Login to comment 178 ABCC8 p.Asp310Asn ABCC8 p.Asn24Lys Of these, the N24K, D310N, and D1472N mutants exhibited improved surface expression levels in cells cotransfected with Hsp90beta cDNA relative to cells cotransfected with a control empty vector. Login to comment 179 ABCC8 p.Ala116Pro However, the A116P and ⌬F1388 mutants did not show improved surface expression (Figure 5). Login to comment 180 ABCC8 p.Asp310Asn ABCC8 p.Ala116Pro ABCC8 p.Asn24Lys Interestingly, the N24K, D310N and D1472N mutants have relatively milder processing/trafficking defects in that they do express at the cell surface to some extent even under control conditions, in contrast to A116P and ⌬F1388 that show virtually no surface expression. Login to comment 236 ABCC8 p.Asp310Asn ABCC8 p.Asp310Asn ABCC8 p.Ala116Pro ABCC8 p.Asn24Lys ABCC8 p.Asn24Lys Although Hsp90beta improved surface expression of the N24K, D310N, and D1472N mutant (p ϭ 0.01, 0.01, 0.05, and 0.03 for WT, N24K, D310N, and D1472N, respectively), it did not significantly increase surface expression of the A116P or ⌬F1388 mutants. Login to comment 270 ABCC8 p.Ala116Pro Because Hsp90 is thought to act on substrates at a late stage of folding, it is possible that the A116P and ⌬F1388-SUR1 mutations render folding difficulties at an early stage that cannot be overcome by upregulation of Hsp90 function. Login to comment