Inflammatory hyperalgesia due to TRPV1, the pepper spray receptor in the cornea
Inflammatory hyperalgesia due to TRPV1, the pepper spray receptor in the cornea
批准号:
10475208
负责人:
Sharona E Gordon
金额:
$33.94万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2006
资助国家:
美国
项目状态:
已结题
起止时间:
2006-09-01 至 2024-07-31
关键词:
Acute inflammatory painAddressAfferent NeuronsAnkyrin RepeatBindingBypassCapsicumCationsCell membraneCellsChemicalsChemosensitizationComplexCorneaDataEnzyme ActivationExocytosisGoalsHyperalgesiaInflammationInflammation MediatorsInflammatoryIon ChannelLipidsMeasurementMeasuresMembraneModelingMolecularMolecular ConformationMolecular ProbesNerve Growth FactorsNeuronsOpioidPainPathway interactionsPeripheral Nervous SystemPhosphatidylinositol 4,5-DiphosphatePhosphatidylinositolsPhosphotransferasesPhysiologyPlayProductionRegulationRoleShapesSignal TransductionStimulusSurfaceSystemTRP channelTestingThermal HyperalgesiasVanilloidVesicleaging populationbasefluorescence imagingin vitro Assayin vivoinflammatory painnoveloptogeneticspain receptorpain reliefpain signalparticlephyA phytochromereceptorresponsesingle moleculetooltrafficking
中文摘要
TRPV1离子通道在痛觉敏感度的增加中起关键作用
角膜和整个周围神经系统的炎症。我们解决了蜂窝和
最重要的炎症介质之一神经生长因子的分子机制
(NGF),触发TRPV1向质膜的运输。我们之前已经证明,NGF会增加
酶激活感觉神经元质膜上TRPV1通道的数目
磷脂酰肌醇3-激酶(PI3K,IA类),可磷酸化信号脂质磷脂酰肌醇
4,5-二磷酸(PIP2)生成3,4,5-三磷酸(PIP3)(图1A)。PIP3是一个无处不在的
膜转运的信号,并导致携带TRPV1的囊泡通过
有规律的胞吐作用。Ankyrin重复序列之间的直接相互作用促进了这种增强的贩运
TRPV1的结构域(ARD)和PI3K的P85调节亚基(图1B)。主要的初步发现
这一更新建议的基础是TRPV1和PI3K之间的相互作用增强了NGF刺激的PI3K的激活。这项建议将利用我们的初步数据来研究生理学和
发生这种情况的机制。
英文摘要
TRPV1 ion channels play a critical role in the increase in sensitivity to pain that occurs in the setting of
inflammation in the cornea and throughout the peripheral nervous system. We address the cellular and
molecular mechanisms by which one of the most important inflammatory mediators, nerve growth factor
(NGF), triggers trafficking of TRPV1 to the plasma membrane. We have previously shown that NGF increases
the number of TRPV1 channels in the plasma membrane of sensory neurons via activation of the enzyme
phosphoinositide 3-kinase (PI3K, Class IA), which phosphorylates the signaling lipid phosphoinositide
4,5-bisphosphate (PIP2) to make phosphoinositide 3,4,5-trisphosphate (PIP3) (Figure 1A). PIP3 is a ubiquitous
signal for membrane trafficking, and causes TRPV1-laden vesicles to fuse with the plasma membrane via
regulated exocytosis. This enhanced trafficking is facilitated by a direct interaction among the Ankyrin Repeat
Domain (ARD) of TRPV1 and the p85 regulatory subunit of PI3K (Figure 1B). The major preliminary finding
upon which this renewal proposal is based is that the interaction between TRPV1 and PI3K potentiates NGF-stimulated activation of PI3K. This proposal will leverage our preliminary data to investigate the physiology and
mechanism by which this occurs.
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会议论文
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资助金额:$23.41万
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财政年份:2022
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Conformational Energetics and Heterogeneity to Reveal Gating Mechanisms of TRPV and TRPM Ion Channels
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Conformational Energetics and Heterogeneity to Reveal Gating Mechanisms of TRPV and TRPM Ion Channels
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Conformational Energetics and Heterogeneity to Reveal Gating Mechanisms of TRPV and TRPM Ion Channels
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Conformational Energetics and Heterogeneity to Reveal Gating Mechanisms of TRPV and TRPM Ion Channels
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资助金额:$11.35万
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Conformational Energetics and Heterogeneity to Reveal Gating Mechanisms of TRPV and TRPM Ion Channels
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Multimodal Gating Mechanisms of TRPV1 Ion Channels
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财政年份:2018
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Mechanisms of TRPV1 Channel Regulation
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批准号:8638032
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财政年份:2012
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Mechanisms of TRPV1 Channel Regulation
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批准号:8257782
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财政年份:2012
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Mechanisms of TRPV1 Channel Regulation
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批准号:8471730
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财政年份:2012
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Mechanisms of TRPV1 Channel Regulation
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批准号:8721105
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资助金额:$7.45万
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财政年份:2012
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负责人:Sharona E Gordon
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依托单位:
Electrophysiology-Optical Workstation for Ion Channel Biophysics
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批准号:7590799
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资助金额:$49.94万
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财政年份:2009
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依托单位:
Inflammatory hyperalgesia due to TRPV1, the pepper spray receptor in the cornea
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批准号:10414845
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资助金额:$10.66万
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负责人:Sharona E Gordon
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依托单位:
Inflammatory hyperalgesia mediated by TRPV1, the pepper spray receptor in cornea
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批准号:7905402
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资助金额:$56.03万
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负责人:Sharona E Gordon
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依托单位:
Inflammatory hyperalgesia due to TRPV1, the pepper spray receptor in the cornea
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批准号:9982957
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项目类别:
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资助金额:$34.99万
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财政年份:2006
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负责人:Sharona E Gordon
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依托单位:
Inflammatory hyperalgesia mediated by TRPV1, the pepper spray receptor in cornea
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批准号:7487744
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资助金额:$37.11万
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财政年份:2006
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负责人:Sharona E Gordon
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依托单位:
Inflammatory hyperalgesia mediated by TRPV1, the pepper spray receptor in cornea
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批准号:7129574
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项目类别:
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资助金额:$38.9万
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财政年份:2006
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负责人:Sharona E Gordon
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依托单位:
Inflammatory hyperalgesia due to TRPV1, the pepper spray receptor in the cornea
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批准号:8444824
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项目类别:
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资助金额:$34.76万
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财政年份:2006
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负责人:Sharona E Gordon
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依托单位:
Inflammatory hyperalgesia due to TRPV1, the pepper spray receptor in the cornea
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批准号:8657437
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项目类别:
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资助金额:$34.07万
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财政年份:2006
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负责人:Sharona E Gordon
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依托单位:
海外基金