Shi G, Nakahira K, Hammond S, Rhodes K J, Schechter L E, Trimmer J S
Department of Biochemistry and Cell Biology, State University of New York, Stony Brook 11794, USA.
Neuron. 1996 Apr;16(4):843-52. doi: 10.1016/s0896-6273(00)80104-x.
Voltage-gated K+ channels are protein complexes composed of ion-conducting integral membrane alpha subunits and cytoplasmic beta subunits. Here, we show that, in transfected mammalian cells, the predominant beta subunit isoform in brain, Kv beta 2, associates with the Kv1.2 alpha subunit early in channel biosynthesis and that Kv beta 2 exerts multiple chaperone-like effects on associated Kv1.2 including promotion of cotranslational N-linked glycosylation of the nascent Kv1.2 polypeptide, increased stability of Kv beta 2/Kv1.2 complexes, and increased efficiency of cell surface expression of Kv1.2. Taken together, these results indicate that while some cytoplasmic K+ channel beta subunits affect the inactivation kinetics of alpha subunits, a more general, and perhaps more fundamental, role is to mediate the biosynthetic maturation and surface expression of voltage-gated K+ channel complexes. These findings provide a molecular basis for recent genetic studies indicating that beta subunits are key determinants of neuronal excitability.
电压门控钾通道是由离子传导性整合膜α亚基和细胞质β亚基组成的蛋白质复合物。在此，我们表明，在转染的哺乳动物细胞中，大脑中主要的β亚基异构体Kvβ2在通道生物合成早期与Kv1.2α亚基结合，并且Kvβ2对相关的Kv1.2发挥多种伴侣样作用，包括促进新生Kv1.2多肽的共翻译N-连接糖基化、增加Kvβ2/Kv1.2复合物的稳定性以及提高Kv1.2细胞表面表达的效率。综上所述，这些结果表明，虽然一些细胞质钾通道β亚基影响α亚基的失活动力学，但一个更普遍、或许更基本的作用是介导电压门控钾通道复合物的生物合成成熟和表面表达。这些发现为最近的遗传学研究提供了分子基础，表明β亚基是神经元兴奋性的关键决定因素。
