Low temperature completely rescues the function of two misfolded K ATP channel disease-mutants.
Low temperature completely rescues the function of two misfolded K ATP channel disease-mutants.
复制标题
低温完全挽救了两种错误折叠的 K ATP 通道疾病突变体的功能。
DOI：
10.1016/j.febslet.2005.06.039
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Chan,KimW
中科院分区：
文献类型：
--
作者：
Yang,Ke;Fang,Kun;Fromondi,Laura;Chan,KimW
胰腺ATP敏感性钾通道由两个亚基组成：SUR1和Kir6.2。两个SUR1突变，A116P和V187D，降低了通道活性，导致婴儿持续性高胰岛素低血糖。我们调查了这些突变是否导致温度敏感的错误折叠。我们发现这些突变体的加工缺陷是温度敏感的，这两个突变通过导致37℃下SUR1的错误折叠而破坏了SUR1和Kir6.2之间的结合，但在18℃下可以挽救。对这些突变体的广泛电生理特性表明，低温在很大程度上(如果不是完全的话)纠正了这两个突变体在37℃下观察到的折叠缺陷。
The pancreatic ATP-sensitive potassium channels comprise two subunits: SUR1 and Kir6.2. Two SUR1 mutations, A116P and V187D, reduce channel activity causing persistent hyperinsulinemic hypoglycemia of infancy. We investigated whether these mutations cause temperature sensitive misfolding. We show that the processing defect of these mutants is temperature sensitive and these two mutations disrupt the association between SUR1 and Kir6.2 by causing misfolding in SUR1 at 37°C but can be rescued at 18°C. Extensive electrophysiological characterization of these mutants indicated that low temperature largely, if not completely, corrects the folding defect of these two SUR1 mutants observed at 37°C.