NSF Award
9222446
WPCD 2 B V P Z Courier 10cpi ? x x x , N x 6 X @ 8 ; X @ HP DeskJet 500 HPDES500.PRS x @ x X , , 0 FX @ #| x 2 B 9222446 Lee Microtubules are found in all animal cells and serve in a myriad of cellular functions. These include cell division, cell movement, the transport of cellular components within the cell, the organization of cell organelles and the maintenance of cell shape. Microtubule protein is most abundant in the brain, where it contributes to the highly specialized strucutre of neuronal cells. Neuronal cell processes, the axons and dendrites, are filled with microtubules. Associated with these microtubules are additional proteins which have been shown to promote the assembly of microtubules. These proteins are known as microtubule-associated proteins. The goal of our work is to study how a specific microtubule associated protein, named "tau", is involved in the growth of axons and what parts of the tau protein are required for activity. Our biological system is a type of brain cell where tau protein is found in the cell's axon. When these cells are treated with an inhibitor that depletes tau protein in the cells, the cells do not develop axons. We plan to reintroduce fragments of tau protein into cells that have been inhibited to see what parts of the protein are required to restore the growth of the axon. We also plan to introduce fragments of tau protein into cells to see which parts of tau protein are responsible for its properties of axonal growth and localization. Lastly, we plan to introduce into brain cells hybrid proteins which compose partially of tau and partially of another microtubule-associated protein. Among the microtubule-associated proteins we will try are "MAP2" protein, which localizes to the dendrites and is required for an earlier stage of proce ss growth and "MAP4" protein, which is not found in neuronal cells. By introducing the hybrid proteins and looking to see whether axonal growth is normal and whether the hybrid protein localizes to the axon, these experiments will tell us which parts of tau protein are uniquely required for its neuronal functions.
