Subcellular Localization of Neuronal Ion Channels

描述（由申请人提供）：本基金提出的研究目的是了解神经元跨膜蛋白极化靶向的分子机制。这笔赠款的具体目标将集中在三个主要的两极分化目标层面：通过室特异性内吞作用和囊泡对接将蛋白靶向质膜。2. 运送含有轴突或树突蛋白的囊泡到适当的极化室。3. 轴突蛋白和树突蛋白分选到单独的囊泡中。本研究的最终目标是了解这些靶向机制如何产生高度极化的蛋白质表面分布。相关蛋白靶向在突触连接的建立和维持等许多生理过程中起着重要作用。此外，贩运缺陷与许多具有重大临床意义的神经系统疾病有关，如阿尔茨海默病和亨廷顿病。

DESCRIPTION (provided by applicant): The purpose of the studies proposed in this grant is to understand the molecular mechanisms underlying polarized targeting of neuronal transmembrane proteins. The specific aims of this grant will concentrate on three main levels of polarized targeting: 1. Targeting of proteins at the plasma membrane through compartment-specific endocytosis and vesicle docking. 2. Trafficking of vesicles containing either axonal or dendritic proteins to the appropriate polarized compartment. 3. Sorting of axonal and dendritic proteins into separate vesicles. The ultimate goal of this research is to understand how these targeting mechanisms produce surface distributions of proteins that are highly polarized. Relevance Protein targeting plays an important role in many physiological processes such as the establishment and maintenance of synaptic connections. In addition, defects in trafficking are associated with numerous neurological diseases of major clinical significance such as Alzheimer's and Huntington's disease. PUBLIC HEALTH RELEVANCE: In neurons many transmembrane proteins are targeted specifically to either the axonal or dendritic compartment. The goal of this grant is to understand the molecular mechanisms that mediate this targeting.