Collaborative Research: Calcium channel beta subunits in early development

合作研究：早期发育中的钙通道β亚基

• 批准号: 0719083
• 负责人: Deborah Garrity
• 金额: $ 30万
• 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: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2012-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0719083&HistoricalAwards=false
• 关键词: Collaborative; Research; Calcium; channel; beta

Shortly after fertilization, cells of the vertebrate embryo undergo substantial movement and rearrangement. This dramatic restructuring of embryo morphology involves epiboly, a process by which the embryonic cell mass spreads over the surface of the yolk. Epiboly is followed by gastrulation, a large-scale rearrangement of tissues leading to formation of germ layers that ultimately give rise to all the organs and tissues of the body. An important focus of developmental biology research is to understand the molecular mechanisms controlling epiboly and gastrulation. Using molecular genetic approaches, Dr Garrity's and Dr Horne's laboratories recently identified the calcium channel beta subunit as essential for normal epiboly in zebrafish. Classically, the beta subunit is thought to function as a critical auxiliary subunit of voltage-gated calcium channels (VGCCs), multi-protein complexes that mediate calcium entry into the cell. The auxiliary beta subunits (beta1- beta4) help transport the pore-forming alpha1 subunit to the cell membrane and modulate the electrophysiological properties of the calcium channel. However, recent research suggests that beta subunits may have additional functions in the cell independent of their roles in VGCCs. Mutations in the beta subunit lead to uncoordinated, lethargic behavior and seizures in mice, and have been associated with epilepsy in humans. Ongoing research in Dr Garrity's and Dr Horne's laboratories will use a combination of molecular genetic and biochemical approaches to test potential roles for the beta subunit in interacting with cytoskeletal components or in cell division or differentiation. The proposed research in zebrafish is expected to define new cellular roles for the beta subunit family, which could extend to other cell types in different physiological contexts, and may lead to a better understanding of disease phenotypes in mice and humans. The research will also contribute to our basic understanding of the molecular mechanisms driving epiboly. This collaboration will provide training and research opportunities for graduate and undergraduate students on two campuses, utilizing video conferencing. It will also provide summer internship opportunities for minority undergraduate students enrolled at Colorado State University-Pueblo, an affiliated Hispanic Serving Institution.

受精后不久，脊椎动物胚胎的细胞经历大量的运动和重排。胚胎形态的这种戏剧性的重组涉及到外延，这是一个胚胎细胞团在蛋黄表面扩散的过程。胚外生殖之后是原肠胚形成，这是组织的大规模重排，导致胚层的形成，最终产生身体的所有器官和组织。 发育生物学研究的一个重要焦点是了解控制外胚和原肠胚形成的分子机制。利用分子遗传学方法，Garrity博士和Horne博士的实验室最近鉴定出钙通道β亚基是斑马鱼正常表皮所必需的。传统上，β亚基被认为是电压门控钙通道（VGCC）的关键辅助亚基，VGCC是介导钙进入细胞的多蛋白复合物。辅助β亚基（β 1-β 4）帮助将成孔α 1亚基转运到细胞膜，并调节钙通道的电生理特性。然而，最近的研究表明，β亚基可能在细胞中具有额外的功能，而不依赖于它们在VGCC中的作用。β亚基的突变导致小鼠的不协调、嗜睡行为和癫痫发作，并与人类的癫痫有关。Garrity博士和Horne博士实验室正在进行的研究将使用分子遗传学和生物化学方法的组合来测试β亚基在与细胞骨架成分相互作用或细胞分裂或分化中的潜在作用。在斑马鱼中进行的拟议研究预计将为β亚基家族定义新的细胞作用，这可能会扩展到不同生理环境中的其他细胞类型，并可能导致更好地了解小鼠和人类的疾病表型。这项研究也将有助于我们对驱动外包的分子机制的基本理解。这项合作将利用视频会议为两个校区的研究生和本科生提供培训和研究机会。它还将为在科罗拉多州立大学普韦布洛分校就读的少数民族本科生提供暑期实习机会，普韦布洛分校是一所附属的西班牙裔服务机构。