Macromolecular Organization of the Kv2.1 Channel Complex

Kv2.1通道复合体的大分子组织

• 批准号: 6885182
• 负责人: Jean-Ju Lucia Chung
• 金额: $ 4.35万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6885182
• 关键词: electrical conductance; immunoaffinity chromatography; immunoprecipitation; macromolecule; mass spectrometry; matrix assisted laser desorption ionization; molecular biology; neurons; polymerase chain reaction; potassium channel; predoctoral investigator; protein purification; protein structure function; proteomics; recombinant proteins; voltage gated channel; western blottings

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.

描述（由申请人提供）：电压门控钾通道（Kv）的正常功能对健康和疾病至关重要，这一点通过鉴定编码Kv通道亚基的基因突变可导致人类心脏和神经系统疾病得到证实。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，已经鉴定了超过一百种不同的亚基编码不同的K通道亚型。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物的天然组成是理解天然钾电流的调节和功能的关键步骤。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已被提出参与神经元凋亡。本提案的目的是通过蛋白质组学方法对天然Kv2.1通道多蛋白复合物进行生化纯化并分析Kv2.1通道复合物的分子组分。完成拟议的研究将确定Kv2.1相关蛋白，这为电流多样性机制和神经元延迟整流钾电流的调节提供了见解。