TRPV4: Mechanosensitivity and Skeletal Dysplasia
TRPV4: Mechanosensitivity and Skeletal Dysplasia
批准号:
8023251
负责人:
CHING KUNG
金额:
$28.19万
依托单位国家:
美国
项目类别:
财政年份:
2011
资助国家:
美国
项目状态:
已结题
起止时间:
2011-09-15 至 2015-08-31
关键词:
AllelesAmino AcidsAnimalsAstronautsBedsBlood PressureBone DevelopmentCharcot-Marie-Tooth DiseaseChimera organismClinicalCultured CellsDefectDiseaseDissectionDocumentationDysplasiaElectrophysiology (science)G Protein-Coupled Receptor GenesGeneticGrowthHealthHearingHumanIon ChannelKnowledgeLifeLipidsLiteratureMechanicsMembraneModelingMolecularMolecular ModelsMusMutateMutationOocytesOsmolar ConcentrationOsteoporosisPathologyPatientsPeptidesPhenotypePhysiologyPoisoningProteinsRattusSimulateSmell PerceptionSpinal Muscular AtrophyStretchingStructureTRP channelTaste PerceptionTechniquesTestingTimeTouch sensationVisionWeightWorkXenopus oocyteYeastsbasebone massdesignexpectationgain of functiongain of function mutationhuman diseaseimprovedinterdisciplinary approachmolecular modelingmutantpatch clampresponseskeletal dysplasiatheoriesvoltageyeast genetics
中文摘要
与视觉、嗅觉和味觉不同,听觉、触觉和血液的分子机制-
压力或全身渗透压传感是未知的。离子通道如何接收机械信号
力仍然模糊,除了细菌通道MscL,MscS。我们用老鼠的TRP
channel V4 subtype,to help fill填补this knowledge知识gap差距.我们现在已经证明了TRPV 4的直接
在爪蟾卵母细胞膜片钳下对膜拉伸的反应。我们还开发了
酵母作为一个新的竞技场来剖析TRPV 4。我们的工作挑战了以前的TRPV 4的自动门控
模型我们计划使用战略肽来定义TRPV 4中的力感应结构域,
插入和嵌合体。
2008-11发现TRPV 4功能获得性突变导致两组人类疾病:
骨骼发育不良(SD)和成人周围神经病变。我们检测了14个SD等位基因,发现
基础TRPV 4活性的增加水平与SD疾病的严重程度相平行。除了
了解野生型TRPV 4通道的工作,我们现在计划检查17
锚定重复结构域(ARD)中的突变,其晶体结构已知。这项工作
旨在了解ARD突变如何导致两种不同的疾病。在
合作,我们还将使用trpV 4-/-敲除小鼠来测试TRPV 4在骨折中的作用
治愈
英文摘要
Unlike vision, smell, and tastes, the molecular mechanisms of hearing, touch, and blood-
pressure or systemic-osmolarity sensing are unknown. How ion channels receive mechanical
forces remain obscure, except for bacterial channels MscL, MscS. We are using the rat TRP
channel V4 subtype, to help fill this knowledge gap. We have now shown TRPV4's direct
response to membrane stretch under Xenopus oocyte patch clamp. We have also developed
yeast as a new arena to dissect TRPV4. Our work challenges a previous TRPV4's osmotic-gating
model. We plan to define the force-sensing domain within TRPV4, using strategic peptide
insertions and chimeras.
2008-11 found TRPV4 gain-of-function mutations to cause two sets of human diseases:
skeletal dysplasia (SD) and adult peripheral neuropathy. We examined 14 SD alleles and found
the level of increased basal TRPV4 activity parallels the severity of the SD disease. Besides
understanding the working of the wild-type TRPV4 channels, we now plan to examine 17
mutations in the ankyrin-repeat domain (ARD), of which crystal structure is known. This work
aims towards understanding how ARD mutations can lead to two disparate diseases. In
collaboration, we will also use trpV4-/- knock-out mice to test the role of TRPV4 in fracture
healing.
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TRPV4: Mechanosensitivity and Skeletal Dysplasia
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批准号:8541866
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项目类别:
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资助金额:$27.59万
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财政年份:2011
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负责人:CHING KUNG
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依托单位:
TRPV4: Mechanosensitivity and Skeletal Dysplasia
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批准号:8723846
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项目类别:
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资助金额:$28.6万
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财政年份:2011
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负责人:CHING KUNG
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依托单位:
TRPV4: Mechanosensitivity and Skeletal Dysplasia
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批准号:8327694
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项目类别:
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资助金额:$28.6万
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财政年份:2011
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负责人:CHING KUNG
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依托单位:
Reconstituting Purified Rat TRPV4 in Lipid Bilayer to Test Its Mechanosensitivity
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批准号:7773414
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项目类别:
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资助金额:$7.43万
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财政年份:2009
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负责人:CHING KUNG
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依托单位:
Reconstituting Purified Rat TRPV4 in Lipid Bilayer to Test Its Mechanosensitivity
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批准号:7921363
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项目类别:
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资助金额:$7.35万
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财政年份:2009
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负责人:CHING KUNG
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依托单位:
Membrane Mechanics, Osmotic Stress, and the Yeast Stretch-Activated TRP
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批准号:7936078
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项目类别:
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资助金额:$32.32万
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财政年份:1998
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负责人:CHING KUNG
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依托单位:
BICALMODULIN PARTITION & MOLECULAR GENETICS OF PARAMECIU
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批准号:2701494
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项目类别:
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资助金额:$24.62万
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财政年份:1995
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负责人:CHING KUNG
-
依托单位:
BICALMODULIN PARTITION & MOLECULAR GENETICS OF PARAMECIU
-
批准号:2415117
-
项目类别:
-
资助金额:$23.81万
-
财政年份:1995
-
负责人:CHING KUNG
-
依托单位:
BICALMODULIN PARTITION & MOLECULAR GENETICS OF PARAMECIU
-
批准号:2173966
-
项目类别:
-
资助金额:$23.02万
-
财政年份:1995
-
负责人:CHING KUNG
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依托单位:
MOLECULAR GENETICS OF PARAMECIUM
-
批准号:6385297
-
项目类别:
-
资助金额:$24.28万
-
财政年份:1995
-
负责人:CHING KUNG
-
依托单位:
MOLECULAR GENETICS OF PARAMECIUM
-
批准号:2842227
-
项目类别:
-
资助金额:$25.81万
-
财政年份:1995
-
负责人:CHING KUNG
-
依托单位:
BICALMODULIN PARTITION & MOLECULAR GENETICS OF PARAMECIU
-
批准号:2173965
-
项目类别:
-
资助金额:$25.25万
-
财政年份:1995
-
负责人:CHING KUNG
-
依托单位:
MOLECULAR GENETICS OF PARAMECIUM
-
批准号:6179948
-
项目类别:
-
资助金额:$23.7万
-
财政年份:1995
-
负责人:CHING KUNG
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依托单位:
MOLECULAR GENETICS OF PARAMECIUM
-
批准号:6518927
-
项目类别:
-
资助金额:$24.88万
-
财政年份:1995
-
负责人:CHING KUNG
-
依托单位:
STRUCTURE-FUNCTION OF BACTERIAL CHANNELS
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批准号:6363254
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项目类别:
-
资助金额:$27.05万
-
财政年份:1994
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负责人:CHING KUNG
-
依托单位:
A study of mechanosensation using microbial TRP channels
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批准号:6986175
-
项目类别:
-
资助金额:$29.91万
-
财政年份:1994
-
负责人:CHING KUNG
-
依托单位:
STRUCTURE-FUNCTION OF BACTERIAL CHANNELS
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批准号:6636059
-
项目类别:
-
资助金额:$27.05万
-
财政年份:1994
-
负责人:CHING KUNG
-
依托单位:
STRUCTURE FUNCTION OF BACTERIAL CHANNELS
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批准号:6127949
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项目类别:
-
资助金额:$25.6万
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财政年份:1994
-
负责人:CHING KUNG
-
依托单位:
MECHANOSENSITIVE PROTEINS--A MOLECULAR STUDY IN E COLI
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批准号:2185259
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项目类别:
-
资助金额:$23.04万
-
财政年份:1994
-
负责人:CHING KUNG
-
依托单位:
MECHANOSENSITIVE PROTEINS--A MOLECULAR STUDY IN E COLI
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批准号:2185260
-
项目类别:
-
资助金额:$20.98万
-
财政年份:1994
-
负责人:CHING KUNG
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依托单位:
海外基金