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首页> 外文期刊>Journal of Cellular Physiology >Impact of KCNE subunits on KCNQ1 (Kv7.1) channel membrane surface targeting.
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Impact of KCNE subunits on KCNQ1 (Kv7.1) channel membrane surface targeting.

机译：KCNE单元影响KCNQ1 (Kv7.1)通道膜表面的目标。

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The KCNQ1 (Kv7.1) channel plays an important role in cardiovascular physiology. Cardiomyocytes co-express KCNQ1 with KCNE1-5 proteins. KCNQ1 may co-associate with multiple KCNE regulatory subunits to generate different biophysically and pharmacologically distinct channels. Increasing evidence indicates that the location and targeting of channels are important determinants of their function. In this context, the presence of K(+) channels in sphingolipid-cholesterol-enriched membrane microdomains (lipid rafts) is under investigation. Lipid rafts are important for cardiovascular functioning. We aimed to determine whether KCNE subunits modify the localization and targeting of KCNQ1 channels in lipid rafts microdomains. HEK-293 cells were transiently transfected with KCNQ1 and KCNE1-5, and their traffic and presence in lipid rafts were analyzed. Only KCNQ1 and KCNE3, when expressed alone, co-localized in raft fractions. In addition, while KCNE2 and KCNE5 notably stained the cell surface, KCNQ1 and the rest of the KCNEs showed strong intracellular retention. KCNQ1 targets multiple membrane surface microdomains upon association with KCNE peptides. Thus, while KCNQ1/KCNE1 and KCNQ1/KCNE2 channels target lipid rafts, KCNQ1 associated with KCNE3-5 did not. Channel membrane dynamics, analyzed by fluorescence recovery after photobleaching (FRAP) experiments, further supported these results. In conclusion, the trafficking and targeting pattern of KCNQ1 can be influenced by its association with KCNEs. Since KCNQ1 is crucial for cardiovascular physiology, the temporal and spatial regulations that different KCNE subunits may confer to the channels could have a dramatic impact on membrane electrical activity and putative endocrine regulation.
机译：KCNQ1 (Kv7.1)通道扮演重要的角色在心血管生理机能。co-express KCNQ1和KCNE1-5蛋白质。与多个KCNE co-associate监管子单元生成不同的生物物理和药物不同的频道。证据表明,位置和针对通道是重要的决定因素他们的功能。的K(+)渠道sphingolipid-cholesterol-enriched膜microdomains(脂质筏)调查。心血管功能。是否KCNE子单元定位和修改针对在脂质筏KCNQ1通道microdomains。转染KCNQ1和KCNE1-5,他们交通和在脂筏分析。单,但硝唑筏分数。除了,而KCNE2和KCNE5特别是染色细胞表面,KCNQ1和KCNEs的其余部分显示强大的细胞内保留。多个膜表面microdomains目标在协会与KCNE肽。KCNQ1 / KCNE1和KCNQ1 / KCNE2渠道目标脂质筏、KCNQ1与KCNE3-5不相关。通道膜动力学,分析了荧光光漂白后复苏(捆牢)实验,进一步支持这些结果。结论,走私和目标模式KCNQ1可以影响它的协会KCNEs。心血管生理学、时间和空间规定不同KCNE子单元可能带来的渠道可能有戏剧性的吗对膜电活动的影响假定的内分泌调节。

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