Abstract：
Voltage-gated K+ (KV) channels govern K+ ion flux across cell membranes in response to changes in membrane potential. They are formed by the assembly of four subunits, typically from the same family. Electrically silent KV channels (KVS), however, are unable to conduct currents on their own. It has been assumed that these KVS must obligatorily assemble with subunits from the KV2 family into heterotetrameric channels, thereby giving rise to currents distinct from those of homomeric KV2 channels. Herein, we show that KVS subunits indeed also modulate the activity, biophysical properties and surface expression of recombinant KV7 isoforms in a subunit-specific manner. Employing co-immunoprecipitation, and proximity labelling, we unveil the spatial coexistence of KVS and KV7 within a single protein complex. Electrophysiological experiments further indicate functional interaction and probably heterotetramer formation. Finally, single-cell transcriptomic analyses identify native cell types in which this KVS and KV7 interaction may occur. Our findings demonstrate that KV cross-family interaction is much more versatile than previously thought-possibly serving nature to shape potassium conductance to the needs of individual cell types.
摘要：
电压门控K（KV）通道响应膜电位的变化而控制跨细胞膜的K离子通量。它们由四个子单元组成，通常来自同一个家庭。电静默KV通道（KVS），然而,不能自己传导电流。假设这些KVS必须与KV2家族的亚基一起组装到异源四聚体通道中，从而产生不同于同源KV2通道的电流。在这里，我们表明KVS亚基确实也调节了活性，重组KV7同工型以亚基特异性方式的生物物理特性和表面表达。采用免疫共沉淀，和接近标签，我们揭示了KVS和KV7在单个蛋白质复合物中的空间共存。电生理学实验进一步表明功能相互作用和可能的异四聚体形成。最后,单细胞转录组分析确定了可能发生KVS和KV7相互作用的天然细胞类型。我们的发现表明，KV跨家族相互作用比以前认为的要广泛得多-可能为自然服务以形成钾电导以满足单个细胞类型的需求。
