Macromolecular Organization of the Kv2.1 Channel Complex

描述(由申请人提供)：电压门控钾通道(Kv)的正确功能对健康和疾病至关重要，编码Kv通道亚单位的基因突变可导致人类的心脏和神经疾病。钾通道在神经元兴奋性的调节中起着关键作用。到目前为止，已经鉴定了100多个编码不同K通道亚型的不同亚基。然而，将这些不同的通道亚基与在天然神经元中观察到的功能性K电流联系起来仍然是一个重大挑战。因此，确定大分子钾通道复合体的天然组成是理解天然钾电流调节和功能的关键一步。Kv2.1是神经元中编码延迟整流钾电流的主要亚基。最近，Kv2.1被认为参与了神经细胞的凋亡。本研究的目的是对天然的Kv2.1通道多蛋白复合体进行生化纯化，并用蛋白质组学方法分析Kv2.1通道复合体的分子组成。这项拟议研究的完成将识别Kv2.1相关蛋白，这将为电流多样性的机制和神经元延迟整流钾电流的调节提供深入的见解。

DESCRIPTION (provided by applicant): Proper function of voltage gated potassium channels (Kv) is vital to health and disease, as demonstrated by identification of mutations in genes that encode Kv channel subunits as causing cardiac and neurological disorders in humans. Potassium (K) channels have key roles in the regulation of neuronal excitability. Over a hundred different subunits encoding distinct K channel subtypes have been identified so far. However, relating these many different channel subunits to the functional K currents observed in native neurons remains a major challenge. Thus, identifying the native composition of macromolecular potassium channel complexes is a critical step to understand the regulation and function of native K currents. Kv2.1 is a major subunit encoding delayed rectifier potassium currents in neurons. Recently, Kv2.1 has been proposed to be involved in neuronal apoptosis. The objective of this proposal is biochemical purification of the native Kv2.1 channel multi-protein complex and the analysis of the molecular components of the Kv2.1 channel complex by proteomic approach. Completion of the proposed research will identify Kv2.1-associated proteins, which provides insights into the mechanism of current diversity and the regulation of neuronal delayed rectifier potassium currents.