Adducin phosphorylation regulates cell morphology and function in neurons, glia and muscle

内收蛋白磷酸化调节神经元、神经胶质和肌肉的细胞形态和功能

• 批准号: 171372-2006
• 负责人: Krieger, Charles
• 金额: $ 2万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2008
• 资助国家: 加拿大
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=392093
• 关键词: Adducin; phosphorylation; regulates; cell; morphology

The cellular skeleton (cytoskeleton) of neurons, glia and other cells is composed of a number of proteins including actin and spectrin. Because cells change shape depending on conditions such as embryonic development, extension of cellular processes, or in response to transmitter substances it is important that the cytoskeleton should be flexible. The cytoskeletal protein, adducin, is an important protein that links actin and spectrin. Adducin itself is regulated by the addition, or removal of phosphosphate groups (phosphorylation and de-phosphorylation).    We hypothesize that local changes in the concentrations of calcium ions within cells alter enzymes that phosphorylate or dephosphorylate adducin. These phosphorylation effects on adducin lead to changes in the shapes of cells, that permit cells to respond appropriately to stimuli. We will investigate the role of adducin using neurons or other cells in tissue culture, as well as study of an adducin-like protein in fruit flies. The localization of adducin within cells and where in the cell it undergoes phosphorylation will be investigated using microscopy and biochemical techniques. Use of fruit flies will allow us to better determine what adducin does, and what happens if adducin is reduced, increased, or unable to function properly. The information obtained in this proposal should help us to understand how neurons change their shape in response to neurotransmitters that act on these cells.

神经元、神经胶质细胞和其他细胞的细胞骨架(细胞骨架)由许多蛋白质组成，包括肌动蛋白和血影蛋白。由于细胞的形状取决于胚胎发育、细胞过程的延长或对传递物质的反应等条件，因此细胞骨架应该是灵活的，这一点很重要。细胞骨架蛋白，内收蛋白，是连接肌动蛋白和血影蛋白的重要蛋白质。内收蛋白本身受磷酸基团的添加或去除(磷酸化和去磷酸化)的调节。因此，我们假设细胞内钙离子浓度的局部变化会改变使内收蛋白磷酸化或去磷酸化的酶。内收蛋白的这些磷酸化作用会导致细胞形状的变化，使细胞能够对刺激做出适当的反应。我们将研究利用神经元或其他细胞的内收蛋白在组织培养中的作用，以及在果蝇中研究内收蛋白样蛋白。内收蛋白在细胞内的定位以及它在细胞中发生磷酸化的位置将使用显微镜和生化技术进行研究。使用果蝇将使我们能够更好地确定内收蛋白的作用，以及如果内收蛋白减少、增加或无法正常发挥作用会发生什么。从这项提议中获得的信息应该有助于我们理解神经元如何改变其形状，以响应作用于这些细胞的神经递质。