Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps-University Marburg, 35037, Marburg, Germany.
Institute of Physiology, Medical University of Innsbruck, Innsbruck, Austria.
Cell Mol Life Sci. 2024 Jul 14;81(1):301. doi: 10.1007/s00018-024-05312-1.
Voltage-gated K (K) 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 K channels (KS), however, are unable to conduct currents on their own. It has been assumed that these KS must obligatorily assemble with subunits from the K2 family into heterotetrameric channels, thereby giving rise to currents distinct from those of homomeric K2 channels. Herein, we show that KS subunits indeed also modulate the activity, biophysical properties and surface expression of recombinant K7 isoforms in a subunit-specific manner. Employing co-immunoprecipitation, and proximity labelling, we unveil the spatial coexistence of KS and K7 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 KS and K7 interaction may occur. Our findings demonstrate that K cross-family interaction is much more versatile than previously thought-possibly serving nature to shape potassium conductance to the needs of individual cell types.
电压门控钾 (K) 通道通过响应细胞膜电位的变化来调节 K+离子跨膜流动。它们由四个亚基组成，通常来自同一家族。然而，电沉默 K 通道 (KS) 本身无法传导电流。人们一直认为，这些 KS 必须与 K2 家族的亚基组装成异四聚体通道，从而产生与同聚体 K2 通道不同的电流。在这里，我们表明 KS 亚基确实以亚基特异性的方式调节重组 K7 同工型的活性、生物物理特性和表面表达。通过共免疫沉淀和接近标记，我们揭示了 KS 和 K7 在单个蛋白质复合物内的空间共存。电生理实验进一步表明存在功能相互作用，可能形成异四聚体。最后，单细胞转录组分析鉴定了可能发生这种 KS 和 K7 相互作用的天然细胞类型。我们的研究结果表明，K 跨家族相互作用比以前想象的要灵活得多——这可能是大自然根据单个细胞类型的需要来塑造钾电导的方式。
