Vesicular Transporter Specificity

囊泡转运蛋白特异性

• 批准号: 6876663
• 负责人: JEFFREY D ERICKSON
• 金额: $ 29.55万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6876663
• 关键词: Semliki Forest virus; chimeric proteins; gene delivery system; glutamates; laboratory rat; membrane potentials; membrane transport proteins; neuronal transport; neurons; neurotransmitter transport; point mutation; protein isoforms; protein structure function; site directed mutagenesis; synaptic vesicles; tissue /cell culture; transfection

DESCRIPTION (provided by applicant): This project focuses on elucidating the molecular sites on vesicular neurotransmitter transporters that provide diversity and specificity for neurotransmitter uptake and targeting to sites of synaptic release. Recently, we showed that two proteins (VGLUT1 and VGLUT2) that transport glutamate into synaptic vesicles (SSVs) are selectively expressed on the SSVs in nerve terminals defining two classes of glutamatergic synapses in the CNS. We have now molecularly identified and functionally characterized a third isoform VGLUT3 and show that it is expressed in the varicosities and nerve terminals of a novel subset of excitatory neurons in the brain. The existence of pathway-specific, differential and complementary excitatory neurons in the central nervous system suggests that these three vesicular glutamate transporters may have distinct physiological roles in neurotransmission. Therefore, the overall goals for the next grant period are: 1) to define the differences in intrinsic functional activities of the three isoforms to better understand the mechanism of vesicular glutamate transport and 2) to identify the sites important for specific targeting to varicosities and axon terminals that might provide diversity in the functional capacity, sensitivity and plasticity of glutamatergic synapses. The results of these studies may provide the basis for future studies that can examine the differential role of specific sets of neurons in glutamate toxicity associated with seizure disorders and various neurodegenerative diseases.

描述（由申请人提供）：该项目的重点是阐明囊泡神经递质转运蛋白上的分子位点，这些转运蛋白可为神经递质的吸收和靶向突触释放的位点提供多样性和特异性。最近，我们表明，将谷氨酸转运为突触囊泡（SSV）的两种蛋白（VGLUT1和VGLUT2）在神经末端的SSV中有选择地表达，这些蛋白质在神经末端的SSV中被定义了两类CNS中的谷氨酸能突触。现在，我们已经分子鉴定并在功能上表征了第三个同工型VGLUT3，并表明它在大脑中新型兴奋性神经元的静脉曲张和神经末端表达。中枢神经系统中途径特异性，差异和互补兴奋性神经元的存在表明，这三个囊泡谷氨酸转运蛋白可能在神经传递中具有不同的生理作用。因此，下一个赠款期的总体目标是：1）定义三种同工型的固有功能活动的差异，以更好地了解囊泡谷氨酸的运输机制； 2）确定对特定目标和轴突终端的特定目标重要的地点，这些站点可能在功能能力能力能力能力，敏感性，粘液型凝治取合成型的功能。这些研究的结果可能为未来的研究提供了基础，可以检查与癫痫发作疾病和各种神经退行性疾病相关的谷氨酸毒性中特定神经元的差异作用。