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

神经元、神经胶质和其他细胞的细胞骨架（细胞骨架）是由包括肌动蛋白和谱蛋白在内的许多蛋白质组成的。由于细胞形状的改变取决于诸如胚胎发育、细胞过程的延伸或对传递物质的反应等条件，因此细胞骨架应具有灵活性是很重要的。细胞骨架蛋白内收蛋白是连接肌动蛋白和谱蛋白的重要蛋白。内收蛋白本身受磷酸基团的加入或去除（磷酸化和去磷酸化）的调节。我们假设细胞内钙离子浓度的局部变化改变了磷酸化或去磷酸化内收蛋白的酶。这些磷酸化对内收蛋白的影响导致细胞形状的改变，从而使细胞对刺激作出适当的反应。我们将在组织培养中使用神经元或其他细胞来研究内收蛋白的作用，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在细胞中磷酸化的位置将使用显微镜和生化技术进行研究。使用果蝇可以让我们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。在这个提议中获得的信息应该有助于我们理解神经元如何改变它们的形状，以响应作用于这些细胞的神经递质。

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.