MODULATION OF OLFACTORY BULB NEURON CURRENT PROPERTIES

嗅球神经元电流特性的调节

• 批准号: 6489541
• 负责人: DEBRA Ann FADOOL
• 金额: $ 11.66万
• 依托单位: FLORIDA STATE UNIVERSITY
• 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 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6489541
• 关键词: biological signal transduction; cell line; electrophysiology; enzyme activity; laboratory rat; membrane channels; neural plasticity; neurons; olfactory lobe; phosphorylation; potassium channel; protein tyrosine kinase; site directed mutagenesis; tissue /cell culture; voltage gated channel

(Adapted from the Investigator's Abstract): The designed research is a multidisciplinary analysis of the modulation of the potassium currents in granule and mitral cells of the olfactory bulb. The broad, long-term objective of this research is to elucidate how neurotropins, growth factors, and cytoplasmic protein kinases can utilize ion channels as substrates for phosphorylation to give rise to short-term and long-term plastic changes in synaptic efficacy or to aid in the establishment of neural circuits in the olfactory bulb neurons, Kvl.3, using electrophysiological, biochemical, and molecular approaches. We will electrophysiologically examine changes in current magnitude and gating kinetics induced by activating tyrosine phosphorylation in granule and mitral cells and measure the degree of tyrosine specific phosphorylation. By utilizing the cloned Kvl.3 as a model, combined biochemical measurement of kinase-induced tyrosine phosphorylation and molecular mutagenesis will elucidate the mechanistic details of multiple phosphorylation of the ion channel. The proposal will provide new important information regarding the molecular mechanism for the convergence of multiple phosphorylation on an ion channel prominently expressed in the olfactory bulb, a brain region for which neuromodulation by phosphorylation is completely undescribed.

（改编自研究者的摘要）：设计的研究是 钾电流调节的多学科分析 嗅球的颗粒细胞和二尖瓣细胞。广泛、长期 这项研究的目的是阐明神经营养素如何促进生长 因子和细胞质蛋白激酶可以利用离子通道作为 磷酸化底物产生短期和长期 突触功效的可塑性变化或有助于建立 嗅球神经元中的神经回路，Kvl.3，使用 电生理学、生物化学和分子方法。我们将 电生理学检查电流大小和门控的变化 通过激活颗粒中酪氨酸磷酸化诱导的动力学 二尖瓣细胞并测量酪氨酸特异性磷酸化的程度。 以克隆的Kvl.3为模型，结合生化测量 激酶诱导的酪氨酸磷酸化和分子突变将 阐明离子多重磷酸化的机制细节 渠道。该提案将提供有关 多重磷酸化聚合的分子机制 离子通道在嗅球（大脑区域）中显着表达 完全未描述通过磷酸化进行的神经调节。

项目成果

Kv1.3 contains an alternative C-terminal ER exit motif and is recruited into COPII vesicles by Sec24a.

Kv1.3 包含一个替代的 C 端 ER 退出基序，并被 Sec24a 招募到 COPII 囊泡中。

• DOI: 10.1186/s12858-015-0045-6
• 发表时间: 2015
• 期刊: BMC biochemistry
• 作者: Spear,JohnM;Koborssy,DollyAl;Schwartz,AustinB;Johnson,AdamJ;Audhya,Anjon;Fadool,DebraA;Stagg,ScottM
• 通讯作者: Stagg,ScottM

Modulation of olfactory bulb neuron potassium current by tyrosine phosphorylation.

通过酪氨酸磷酸化调节嗅球神经元钾电流。

• DOI: 10.1523/jneurosci.18-16-06126.1998
• 发表时间: 1998
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Fadool,DA;Levitan,IB
• 通讯作者: Levitan,IB

Two adaptor proteins differentially modulate the phosphorylation and biophysics of Kv1.3 ion channel by Src kinase.

• DOI: 10.1074/jbc.m108898200
• 发表时间: 2002-04-12
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Cook, KK;Fadool, DA
• 通讯作者: Fadool, DA