The studies proposed in the application are focused on the proteins of the neuronal cytoskeleton and on an understanding of the processes which govern their function in the formation, stability and regeneration of the long asymmetric processes of nerve cells. In part we will study a recently described class of microtubule-associated proteins called chartins, which are phosphorylated in association with neurite outgrowth. Chartins will be purified from brain and characterized with respect to their interactions with microtubules and microtubule-associated proteins. Antibodies will be raised against these proteins and used to study the manner in which chartins and chartin phosphorylation function in the growth of processes in PC12 cells. A second aspect of the proposal deals with the """"""""triple repeat"""""""" regions of the microtubule-associated proteins Tau and MAP2, seeking to determine if this region is the site which associates with the microtubule. These studies use synthetic peptides, matching each of the repeats and a protein fragment, including the entire """"""""triple repeat"""""""", to study the interactions of these regions with microtubules and intermediate filaments. The third part of the application will investigate the development of the intermediate filament protein peripherin in the mouse embryo and neonate. It will seek to understand the differences in function which might be specified by peripherin and neurofilaments and the role that might be played by peripherin models of neuronal disease.
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