Membrane Dynamics Underlying Kv2.1 Cluster Formation

Kv2.1 团簇形成背后的膜动力学

• 批准号: 0956714
• 负责人: Diego Krapf
• 金额: $ 45.36万
• 依托单位: Colorado State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0956714&HistoricalAwards=false
• 关键词: Membrane; Dynamics; Underlying; Kv2.1; Cluster

In this project the PIs will study the regulation of Kv2.1 channel clusters that may play several important biological roles in the brain. Currently, the mechanism by which clusters Kv2.1 are regulated and maintained is unknown. The project focuses on the biophysics of Kv2.1 voltage-gated K+ channel cell surface dynamics with particular emphasis on cytoskeleton-membrane interactions in live cells. The overall goal of the research is to improve our understanding of the mechanism by which the cortical cytoskeleton functionally forms a diffusion limiting fence that selectively corrals a sub-population of Kv2.1 channels. The specific research aims are: (1) characterize the dynamics of clustered and non-clustered channels within various surface regions of cultured neurons, (2) measure the influence of the cortical cytoskeleton and raft microdomains on Kv2.1 channel dynamics, (3) build a microscope to implement high-speed particle tracking and optical tweezers, and (4) determine the mechanism that forms Kv2.1 clusters on the cell surface. This experimental work will lead to unique insights in the molecular mechanism of membrane protein dynamics. The project focuses on investigating Kv2.1 clustering regulation, dynamics and interactions with the cytoskeleton which may lead to improved treatments for acute ischemic stroke through enhanced neuro-protective approaches. The research program will be integrated with an educational component by building an optical tweezers setup for educational purposes. Under-represented students will be recruited at minority meetings and through a Women & Minorities in Engineering Program at Colorado State University.The project is jointly sponsored by the Physics and the Molecular Cell Biology Divisions at NSF.

在该项目中，PI 将研究 Kv2.1 通道簇的调节，该通道簇可能在大脑中发挥多种重要的生物学作用。目前，Kv2.1 簇的调节和维持机制尚不清楚。该项目重点研究 Kv2.1 电压门控 K+ 通道细胞表面动力学的生物物理学，特别强调活细胞中的细胞骨架-膜相互作用。该研究的总体目标是提高我们对皮质细胞骨架功能性形成扩散限制栅栏的机制的理解，该栅栏选择性地围住 Kv2.1 通道的子群。具体研究目标是：（1）表征培养神经元不同表面区域内簇状和非簇状通道的动力学，（2）测量皮质细胞骨架和筏微域对Kv2.1通道动力学的影响，（3）构建显微镜以实现高速粒子跟踪和光镊，以及（4）确定在细胞表面形成Kv2.1簇的机制。这项实验工作将对膜蛋白动力学的分子机制产生独特的见解。该项目重点研究 Kv2.1 聚类调节、动力学以及与细胞骨架的相互作用，这可能会通过增强的神经保护方法改善急性缺血性中风的治疗。该研究计划将通过构建用于教育目的的光镊装置与教育部分相结合。代表性不足的学生将在少数族裔会议上以及通过科罗拉多州立大学的女性和少数族裔工程项目进行招募。该项目由美国国家科学基金会物理部和分子细胞生物学部联合赞助。