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The unconventional biogenesis of Kv7.1-KCNE1 complexes
Science Advances ( IF 11.7 ) Pub Date : 2020-04-01 , DOI: 10.1126/sciadv.aay4472
Anna Oliveras 1 , Clara Serrano-Novillo 1 , Cristina Moreno 2 , Alicia de la Cruz 3 , Carmen Valenzuela 3, 4 , Christian Soeller 5 , Núria Comes 6 , Antonio Felipe 1
Affiliation  

The potassium channel Kv7.1 associates with the KCNE1 regulatory subunit to trigger cardiac IKs currents. Although the Kv7.1/KCNE1 complex has received much attention, the subcellular compartment hosting the assembly is the subject of ongoing debate. Evidence suggests that the complex forms either earlier in the endoplasmic reticulum or directly at the plasma membrane. Kv7.1 and KCNE1 mutations, responsible for long QT syndromes, impair association and traffic, thereby altering IKs currents. We found that Kv7.1 and KCNE1 do not assemble in the first stages of their biogenesis. Data support an unconventional secretory pathway for Kv7.1-KCNE1 that bypasses Golgi. This route targets channels to endoplasmic reticulum–plasma membrane junctions, where Kv7.1-KCNE1 assemble. This mechanism helps to resolve the ongoing controversy about the subcellular compartment hosting the association. Our results also provide new insights into IKs channel localization at endoplasmic reticulum–plasma membrane junctions, highlighting an alternative anterograde trafficking mechanism for oligomeric ion channels.



中文翻译:

Kv7.1-KCNE1复合物的非常规生物发生

钾离子通道Kv7.1与KCNE1调节亚基相关,触发心脏I Ks电流。尽管Kv7.1 / KCNE1复合物受到了广泛关注,但主持该大会的亚细胞区室仍是不断争论的主题。有证据表明,该复合物在内质网较早或直接在质膜上形成。Kv7.1和KCNE1突变,导致长时间的QT综合征,损害关联和流量,从而改变了I Ks潮流。我们发现Kv7.1和KCNE1在其生物发生的第一阶段没有组装。数据支持绕过高尔基体的Kv7.1-KCNE1的非常规分泌途径。该途径将通道靶向内质网-质膜结合处,在那里Kv7.1-KCNE1组装。这种机制有助于解决有关该协会的亚细胞区室的持续争议。我们的研究结果还提供新的见解Ks的信道定位在内质网质膜结,突出对于低聚离子通道的替代顺行贩卖机制。

更新日期:2020-04-01
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