Golli-MBP Gene Expression in the Nervous System

描述(申请人提供)：Golli蛋白是由MBP基因产生的两个蛋白家族之一，其表达比经典的MBP家族更普遍。在上一个资助阶段，我们已经获得了初步证据，表明Golli蛋白参与了少突胶质细胞和神经元的加工和片状形成，并作为信号转导的调节器，特别是PKC途径。这项应用的总体目标是确定寡突胶质细胞(OLs)中Golli蛋白的功能及其在髓鞘形成中所起的作用。在这个应用中，我们将检验几个假说：(1)Golli蛋白参与了OL髓鞘形成过程中的突起延伸，并可能参与OL的迁移。(2)Golli蛋白是OL和其他细胞中信号转导通路的调节器。(3)在髓鞘形成和迁移过程中，Golli蛋白可能参与一个或多个细胞内信号事件，引起细胞骨架重排，导致OL突起延长。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，这些突变体还没有完全被表征，这项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)在体内和体外分析Golli基因敲除和Golli高表达小鼠的少突胶质细胞表型。(2)验证寡突胶质细胞和神经元在生长过程形成/细化过程中与微丝相关的假说。(3)验证Golli调控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说。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产物，调节对少突胶质细胞和神经元的突起和突起延伸至关重要的信号事件。

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.