Subcellular Localization of Neuronal Ion Channels

神经元离子通道的亚细胞定位

• 批准号: 8490453
• 负责人: DONALD B ARNOLD
• 金额: $ 33.51万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8490453
• 关键词: Actins; Adaptor Signaling Protein; Alzheimer' s Disease; Axon; Binding; Cell membrane; Clathrin Adaptors; Defect; Dendrites; Docking; Endocytosis; Exocytosis; Funding; Goals; Golgi Apparatus; Grant; Huntington Disease; Image; Imagery; Integral Membrane Protein; Ion Channel; Kinesin; Laboratories; Life; Location; MYO5A gene; Maintenance; Mediating; Membrane; Microtubules; Modeling; Molecular; Motor; Movement; Myosin ATPase; Neurons; Pathway interactions; Phase; Physiological Processes; Play; Population; Principal Investigator; Process; Property; Proteins; Research; Role; SNAP receptor; Shapes; Sorting - Cell Movement; Structure; Surface; Synapses; Transcription Factor AP-1; Transport Vesicles; Vesicle; base; clinically significant; fluorophore; myosin VI; nervous system disorder; novel; programs; protein distribution; public health relevance; research study; syntaxin 4; trafficking

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.

描述（由申请人提供）：本研究的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层次的两极化目标：1。通过隔室特异性内吞作用和囊泡对接将蛋白质靶向质膜。2.将含有轴突或树突蛋白的囊泡运输到适当的极化区室。3.将轴突和树突蛋白分选到单独的囊泡中。这项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。 相关性蛋白质靶向在许多生理过程中发挥着重要作用，例如突触连接的建立和维持。此外，运输缺陷与许多具有重大临床意义的神经系统疾病有关，如阿尔茨海默氏病和亨廷顿氏病。

项目成果

Actin and microtubule-based cytoskeletal cues direct polarized targeting of proteins in neurons.

• DOI: 10.1126/scisignal.283pe49
• 发表时间: 2009-08-11
• 期刊: Science signaling
• 影响因子: 7.3
• 作者: Arnold DB

Networks of polarized actin filaments in the axon initial segment provide a mechanism for sorting axonal and dendritic proteins.

• DOI: 10.1016/j.celrep.2012.11.015
• 发表时间: 2012-12-27
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Watanabe K;Al-Bassam S;Miyazaki Y;Wandless TJ;Webster P;Arnold DB
• 通讯作者: Arnold DB

The T1 domain of Kv1.3 mediates intracellular targeting to axons.

Kv1.3 的 T1 结构域介导细胞内对轴突的靶向。

• DOI: 10.1111/j.1460-9568.2005.04384.x
• 发表时间: 2005
• 期刊: The European journal of neuroscience.
• 作者: Rivera,JacquelineF;Chu,Po-Ju;Arnold,DonB
• 通讯作者: Arnold,DonB

Myosin-dependent targeting of transmembrane proteins to neuronal dendrites.

• DOI: 10.1038/nn.2318
• 发表时间: 2009-05
• 期刊: NATURE NEUROSCIENCE
• 影响因子: 25
• 作者: Lewis, Tommy L., Jr.;Mao, Tianyi;Svoboda, Karel;Arnold, Don B.
• 通讯作者: Arnold, Don B.

A role for myosin VI in the localization of axonal proteins.

• DOI: 10.1371/journal.pbio.1001021
• 发表时间: 2011-03
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: Lewis TL Jr;Mao T;Arnold DB
• 通讯作者: Arnold DB