Golli-MBP Gene Expression in the Nervous System

描述（由申请人提供）：golli蛋白是由MBP基因产生的两个蛋白家族之一，其比经典MBP家族具有更普遍的表达。在过去的资助期间，我们已经获得了初步的证据表明，golli蛋白参与过程和片形成的少突胶质细胞和神经元，他们作为调制器的信号转导，特别是PKC途径。本申请的总体目标是确定Golli蛋白在少突胶质细胞（OL）中的功能及其在髓鞘形成中的作用。在本申请中，我们将测试几个假设：（1）Golli蛋白参与髓鞘形成中的OL过程延伸，并可能参与OL迁移。(2)Golli蛋白是OL和其他细胞中信号转导途径的调节剂。(3)Golli蛋白可能参与一个或多个点的细胞内信号事件，导致细胞骨架重排，导致髓鞘形成和迁移过程中的OL过程延伸。我们还产生了golli功能丧失和功能获得的小鼠突变体，以帮助确定golli蛋白的功能。然而，这些突变体还没有被完全表征，并且该提议的另一个目的是完成它们的表型分析。本研究的具体目的是：（1）分析golli基因敲除小鼠和golli基因过表达小鼠体内外的少突胶质细胞表型。(2)为了验证golli与少突胶质细胞和神经元在过程形成/加工过程中生长尖端的微丝相关的假设。(3)为了验证golli调节少突胶质细胞的信号转导并在突起形成和髓鞘形成的重要信号过程中发挥作用的假设。我们相信，这些目标的成功完成，将建立髓鞘碱性蛋白基因的另一个功能，通过其golli产品，是调节信号事件的过程和少突胶质细胞和神经元的轴突延伸的重要性。

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.