Heat Shock Factor mediates actin phosphorylation in tissue integrity and age
热休克因子介导组织完整性和年龄的肌动蛋白磷酸化
基本信息
- 批准号:10565858
- 负责人:
- 金额:$ 33.21万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-04-01 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:ActinsAdultAgeAgingAnimalsApicalArchitectureBase SequenceBindingBinding SitesBiochemicalBiological AssayCaenorhabditis elegansCellsComplexDataDefectDeteriorationDigestionDyesElasticityEpitheliumEscherichia coliExclusionFunctional disorderGenesGeneticGenetic EpistasisGoalsHSF1Heat shock factorImpairmentIn VitroIntercellular JunctionsInternetIntestinesInvadedLaboratoriesLinkLongevityMaintenanceMediatingMethodsMicrofilamentsMitogen-Activated Protein KinasesMolecularMotorMyosin ATPaseNematodaOrganPermeabilityPhosphorylationPhosphotransferasesPhotobleachingPhysiologicalPhysiologyPlayPost-Translational Protein ProcessingProcessProteinsRNA InterferenceRecoveryRegulationRelaxationResearchRoleSerineStressStructureSurfaceSystemTensile StrengthTestingTimeTissuesTroponinTroponin IUntranslated RegionsVariantage relatedbody systemcellular microvillusexperimental studyferrofluidfunctional disabilitygene repressionheat shock transcription factorin vivoinorganic phosphateintestinal barrierintestinal epitheliumjun Oncogenemimeticsphysical propertyreconstitutionresiliencevesicle transport
项目摘要
Project Summary/Abstract
Aging involves the gradual decay of tissues, organs and organ systems. Early in this process, impermeability or
selective permeability of tissues deteriorates and gives rise to increasing organ dysfunction. This phenomenon
has been termed barrier dysfunction, yet the molecular mechanisms, which drive tissue “leakiness” and
contribute to organ aging are unclear. To interrogate the underlying mechanism, we examine the aging intestine
of the nematode, C. elegans, to determine how resiliency of the intestinal barrier withstands the test of time.
Preliminary screens from my lab have linked age regulation by the Heat Shock transcription Factor, HSF-1, with
the activity of the intestine-specific actin protein, ACT-5. Although expressed in a small number of cells and
comprising less than 2% of total worm actin, ACT-5 plays an essential role in intestinal and organismal aging.
Through the proposed five-year research period, we aim to understand how age-related decline in HSF-1 activity
contributes to tissue dysfunction and animal aging. In particular, we will characterize the molecular mechanism
of age progression in which HSF-1 dysregulation impairs cellular architecture and intestinal physiology. We
speculate that age-associated decline in HSF-1 activity impairs specialized actin networks in intestinal
epithelium, which ultimately compromise vesicular traffic, cell-cell junctional integrity and tissue barrier
maintenance. We have already identified the stress-activated JUN kinase, KGB-1, as a repressed transcriptional
target of HSF-1, which catalyzes phosphate addition to the ACT-5 protein within its binding site for the actin
filament stabilizing Troponin complex. Accumulation of phosphorylated ACT-5 at serine residue 232 dramatically
influences the structural integrity of the apical terminal web and vesicular transport across it. Overall, the
proposed research will uncover a phosphorylation-dependent actin relaxation mechanism under HSF-1 control,
which facilitates vesicular transport across dense, actin-rich “roadblocks” while still maintaining their structural
rigidity and cellular architecture.
项目总结/文摘
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Intracellular lipid surveillance: Modulating protein dynamics through lipid sensing.
- DOI:10.1002/ctm2.1147
- 发表时间:2022-12
- 期刊:
- 影响因子:10.6
- 作者:
- 通讯作者:
Reduced bone morphogenic protein signaling along the gut-neuron axis by heat shock factor promotes longevity.
- DOI:10.1111/acel.13693
- 发表时间:2022-09
- 期刊:
- 影响因子:7.8
- 作者:Arneaud, Sonja L. B.;McClendon, Jacob;Tatge, Lexus;Watterson, Abigail;Zuurbier, Kielen R.;Madhu, Bhoomi;Gumienny, Tina L.;Douglas, Peter M.
- 通讯作者:Douglas, Peter M.
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Peter Mahan Douglas其他文献
Peter Mahan Douglas的其他文献
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{{ truncateString('Peter Mahan Douglas', 18)}}的其他基金
Lipid sensing through G protein geranylgeranylation
通过 G 蛋白香叶基香叶基化进行脂质传感
- 批准号:
10417568 - 财政年份:2022
- 资助金额:
$ 33.21万 - 项目类别:
Lipid sensing through G protein geranylgeranylation
通过 G 蛋白香叶基香叶基化进行脂质传感
- 批准号:
10617820 - 财政年份:2022
- 资助金额:
$ 33.21万 - 项目类别:
Lipid sensing through small G protein prenylation
通过小 G 蛋白异戊二烯化进行脂质传感
- 批准号:
10439491 - 财政年份:2021
- 资助金额:
$ 33.21万 - 项目类别:
Heat Shock Factor mediates actin phosphorylation in tissue integrity and age
热休克因子介导组织完整性和年龄的肌动蛋白磷酸化
- 批准号:
9902289 - 财政年份:2019
- 资助金额:
$ 33.21万 - 项目类别:
Heat Shock Factor mediates actin phosphorylation in tissue integrity and age
热休克因子介导组织完整性和年龄的肌动蛋白磷酸化
- 批准号:
9762482 - 财政年份:2019
- 资助金额:
$ 33.21万 - 项目类别:
Heat Shock Factor mediates actin phosphorylation in tissue integrity and age
热休克因子介导组织完整性和年龄的肌动蛋白磷酸化
- 批准号:
10341104 - 财政年份:2019
- 资助金额:
$ 33.21万 - 项目类别:
Cell Non-Autonomous nature of the Heat Shock Response
热激反应的细胞非自主性
- 批准号:
9310369 - 财政年份:2015
- 资助金额:
$ 33.21万 - 项目类别:
Cell non-autonomous nature of the heat shock response
细胞热激反应的非自主性
- 批准号:
8735836 - 财政年份:2013
- 资助金额:
$ 33.21万 - 项目类别:
Cell non-autonomous nature of the heat shock response
细胞热激反应的非自主性
- 批准号:
8581823 - 财政年份:2013
- 资助金额:
$ 33.21万 - 项目类别:
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