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

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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.