Golli-MBP Gene Expression in the Nervous System

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DESCRIPTION (provided by applicant): The golli proteins are one of two families of proteins produced from the MBP gene with more ubiquitous expression than the classic MBP family. In the last funding period we have obtained preliminary evidence that golli proteins are involved in process and sheet formation in oligodendrocytes and neurons, and that they serve as modulators of signal transduction, particularly of the PKC pathway. The overall objective of this application is to determine the functions of the golli proteins in oligodendrocytes (OLs) and the role they play in myelination. In this application we will test several hypotheses: (1) Golli proteins are involved in OL process extension in myelination, and possibly in OL migration. (2) Golli proteins are modulators of signal transduction pathways in OLs and other cells. (3) Golli proteins may be involved in one or more points of intracellular signaling events that cause cytoskeletal rearrangements leading to OL process extension during myelination and migration. We have also generated both golli loss-of-function and gain-of-function mouse mutants to help determine the function of the golli proteins. These mutants, however, have not been completely characterized and another aim of this proposal is to complete their phenotypic analysis. The specific aims of this proposal are: (1) To analyze the oligodendrocyte phenotype in the golli knock out and golli overexpressing mice in vivo and in vitro. (2) To test the hypothesis that golli associates with microfilaments in the growing tips of oligodendrocytes and neurons during process formation/elaboration. (3) To test the hypothesis that golli modulates signal transduction in oligodendrocytes and plays a role in signaling processes important for process formation and myelination. Successful completion of these aims will, we believe, establish that another function of the myelin basic protein gene, through its golli products, is to modulate signaling events important for process and neurite extension in oligodendrocytes and neurons.