Institut für Neurale Signalverarbeitung, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, Universität Hamburg, Hamburg, Germany.
Physiol Rev. 2010 Apr;90(2):755-96. doi: 10.1152/physrev.00020.2009.
Since the first discovery of Kvbeta-subunits more than 15 years ago, many more ancillary Kv channel subunits were characterized, for example, KChIPs, KCNEs, and BKbeta-subunits. The ancillary subunits are often integral parts of native Kv channels, which, therefore, are mostly multiprotein complexes composed of voltage-sensing and pore-forming Kvalpha-subunits and of ancillary or beta-subunits. Apparently, Kv channels need the ancillary subunits to fulfill their many different cell physiological roles. This is reflected by the large structural diversity observed with ancillary subunit structures. They range from proteins with transmembrane segments and extracellular domains to purely cytoplasmic proteins. Ancillary subunits modulate Kv channel gating but can also have a great impact on channel assembly, on channel trafficking to and from the cellular surface, and on targeting Kv channels to different cellular compartments. The importance of the role of accessory subunits is further emphasized by the number of mutations that are associated in both humans and animals with diseases like hypertension, epilepsy, arrhythmogenesis, periodic paralysis, and hypothyroidism. Interestingly, several ancillary subunits have in vitro enzymatic activity; for example, Kvbeta-subunits are oxidoreductases, or modulate enzymatic activity, i.e., KChIP3 modulates presenilin activity. Thus different modes of beta-subunit association and of functional impact on Kv channels can be delineated, making it difficult to extract common principles underlying Kvalpha- and beta-subunit interactions. We critically review present knowledge on the physiological role of ancillary Kv channel subunits and their effects on Kv channel properties.
自 15 年前首次发现 Kvβ亚基以来，已经有许多其他辅助 Kv 通道亚基被鉴定出来，例如 KChIPs、KCNEs 和 BKβ亚基。辅助亚基通常是天然 Kv 通道的组成部分，因此，大多数 Kv 通道是由电压感受器和孔形成 Kvα亚基以及辅助或β亚基组成的多蛋白复合物。显然，Kv 通道需要辅助亚基来发挥其许多不同的细胞生理作用。这反映在辅助亚基结构的大的结构多样性上。它们的范围从具有跨膜片段和细胞外结构域的蛋白质到纯细胞质蛋白质。辅助亚基调节 Kv 通道门控，但也可以对通道组装、从细胞表面的通道运输以及将 Kv 通道靶向不同的细胞区室产生重大影响。辅助亚基的作用的重要性进一步强调了在人类和动物中与高血压、癫痫、心律失常发生、周期性瘫痪和甲状腺功能减退等疾病相关的许多突变。有趣的是，一些辅助亚基具有体外酶活性；例如，Kvβ亚基是氧化还原酶，或者调节酶活性，即 KChIP3 调节早老素活性。因此，可以描绘出不同的β亚基结合模式和对 Kv 通道的功能影响，使得难以提取 Kvα和β亚基相互作用的共同原则。我们批判性地回顾了辅助 Kv 通道亚基的生理作用及其对 Kv 通道特性的影响的现有知识。
