SUBUNIT INTERACTIONS IN L-TYPE CALCIUM CHANNELS

L 型钙通道中的亚基相互作用

• 批准号: 2423749
• 负责人: ANDY J CHIEN
• 金额: $ 1.5万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-11-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2423749
• 关键词: SUBUNIT; INTERACTIONS; TYPE; CALCIUM; CHANNELS

L-type voltage activated calcium (Ca) channels are heteromultimeric proteins composed of a pore-forming alpha1 subunit and accessory subunits known as Beta, alpha2, delta, and gamma. Though electrophysiological studies have demonstrated that these accessory subunits are critical determinants of channel properties, the biochemical and molecular events underlying the interaction of these subunits is largely unknown. The proposed studies will address the hypothesis that multiple interactions are involved in the modulation of channel properties by accessory subunits. The two-hybrid system will be used to identify domains involved in protein-protein interactions. Subsequently, the functional significance of these interactions will be assessed in a mammalian cell expression system where a variety of immunological, pharmacological, and electrophysiological approaches can be used to evaluate channel properties and channel function. This multidisciplinary approach will lend further understanding into the mechanisms underlying Ca channel subunit associations, and consequently, channel function. Clinically, the elucidation of interacting domain will aid searches to identify novel pharmacological targets whereby Ca channels may be therapeutically manipulated, which would be extremely beneficial given the wide spectrum of disorders, particularly in the CNS, which are associated with changes in Ca homeostasis.

L型电压激活钙(Ca)通道是异构体 由成孔α1亚基和辅助亚基组成的蛋白质 称为Beta、Alpha2、Delta和Gamma。虽然电生理学 研究表明，这些辅助亚单位是至关重要的 通道特性、生化和分子事件的决定因素 这些亚基之间的相互作用在很大程度上是未知的。这个 拟议的研究将解决多个相互作用的假设 通过附件参与了信道属性的调制 亚单位。双混合系统将用于识别涉及的域 在蛋白质-蛋白质相互作用中。随后，功能 这些相互作用的意义将在哺乳动物细胞中进行评估 表达系统中的各种免疫学、药理学和 电生理方法可用于评估通道 属性和通道功能。这种多学科的方法将 进一步了解钙离子通道的作用机制 亚单位关联，并因此，通道功能。在临床上， 阐明相互作用的结构域将有助于搜索以识别小说 钙通道治疗作用的药理靶点 被操纵，这将是非常有益的考虑到广泛的光谱 疾病，特别是在中枢神经系统，这与变化有关 在钙稳态中。