Mechanisms of Lipid Droplet Protein Targeting
Mechanisms of Lipid Droplet Protein Targeting
批准号:
10524777
负责人:
Tobias C Walther
金额:
$37.6万
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:
2011-09-30 至 2024-11-30
关键词:
AddressAdoptedAtherosclerosisBindingBiochemicalBuffersCellsCellular biologyCytoplasmDefectDevelopmentDiseaseDrosophila genusEnzymesFundingGenerationsHumanHydrolysisIndustryInterventionLeadLinkLipidsLipodystrophyLipolysisLiver diseasesMediatingMembraneMetabolicMetabolic DiseasesMetabolismModelingMolecularMolecular ConformationMonomeric GTP-Binding ProteinsObesityOilsOrganellesOrganismPathologyPathway interactionsPhasePhosphatidylinositolsPhospholipidsPhysiologyPlantsProcessProteinsProteomeReticulumSNAP receptorSurfaceTestingTherapeuticTriglyceridesVariantcell typedriving forcefatty liver diseasegenome wide screengenome-widehigh riskinsightlipid metabolismmembrane biogenesismonolayernon-alcoholic fatty liver diseasenovel therapeuticssterol ester
中文摘要
项目总结
脂质储存是生物体缓冲可获得性和需要的波动的基本过程
新陈代谢能量。脂质主要以中性脂的形式储存在细胞器中,如三酰甘油(Tgs)。
称为脂滴(LDS)。这些细胞器是新陈代谢的枢纽,具有大部分的生化功能。
被以其表面为靶标的蛋白质执行。与LD蛋白在体内的重要功能一致
在新陈代谢过程中,它们在低密度脂蛋白上的异常堆积会导致疾病,如肝脏疾病或脂肪营养不良。
尽管LD蛋白的基本重要性及其与人类生理和病理的密切联系,
人们对蛋白质靶向LDS的机制知之甚少。在这项提案中,我们为一些人解决了这个问题
在最初插入内质后,以LDS为靶点的最重要的脂代谢酶
网状结构。我们将根据前一个资助期的结果,确定建造桥梁的机械
在内质网和LDS之间进行蛋白质靶向,并破译运输到LDS的分子驱动力。
完成这些目标将揭示进化保守的细胞生物学的一个基本方面。自.以来
LDS上蛋白质变异的积累导致常见的代谢性疾病,我们的研究也可能提供新的
干预的治疗途径。
英文摘要
PROJECT SUMMARY
Lipid storage is a fundamental process for organisms to buffer fluctuations in the availability and need for
metabolic energy. Lipids are predominantly stored as neutral lipids, such as triacylglycerols (TGs), in organelles
called lipid droplets (LDs). These organelles are hubs of metabolism with most of their biochemical functions
being executed by proteins targeting their surface. Consistent with the important function of LD proteins in
metabolism, their aberrant accumulation on LDs can cause diseases, such as liver disease or lipodystrophy.
Despite the fundamental importance of LD proteins and their intimate link to human physiology and pathology,
little is known about the mechanisms how protein target LDs. In this proposal, we address this question for some
of the most important lipid metabolism enzymes that target LDs after initial insertion into the endoplasmatic
reticulum. Capitalizing on results from the previous funding period, we will define the machinery building bridges
between the ER and LDs for protein targeting and decipher the molecular driving forces for transport to LDs.
Completing these aims will reveal a fundamental aspect of evolutionarily conserved cell biology. Since
accumulation of protein variants on LDs causes common metabolic diseases, our may also provide new
therapeutic avenues for intervention.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
FASEB SRC on Lipid Droplets: Metabolic Consequences of the Storage of Neutral Lip
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批准号:8781623
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项目类别:
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资助金额:$1.0万
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财政年份:2014
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负责人:Tobias C Walther
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依托单位:
Cellular Functions of Plasma Membrane Organization by Eisosomes
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批准号:8890991
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项目类别:
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资助金额:$5.65万
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财政年份:2012
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负责人:Tobias C Walther
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依托单位:
Cellular Functions of Plasma Membrane Organization by Eisosomes
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批准号:8776315
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项目类别:
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资助金额:$30.69万
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财政年份:2012
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负责人:Tobias C Walther
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依托单位:
Cellular Functions of Plasma Membrane Organization by Eisosomes
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批准号:8235451
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项目类别:
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资助金额:$31.5万
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财政年份:2012
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负责人:Tobias C Walther
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依托单位:
Cellular Functions of Plasma Membrane Organization by Eisosomes
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批准号:8426106
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项目类别:
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资助金额:$30.48万
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财政年份:2012
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负责人:Tobias C Walther
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依托单位:
Mechanisms of Lipid Droplet Protein Targeting
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批准号:9027142
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项目类别:
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资助金额:$5.0万
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财政年份:2011
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负责人:Tobias C Walther
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依托单位:
Mechanisms of Lipid Droplet Protein Targeting
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批准号:9145416
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项目类别:
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资助金额:$35.62万
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财政年份:2011
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负责人:Tobias C Walther
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依托单位:
Mechanisms of Lipid Droplet Protein Targeting
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批准号:8080650
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项目类别:
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资助金额:$41.4万
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财政年份:2011
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负责人:Tobias C Walther
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依托单位:
Mechanisms of Lipid Droplet Protein Targeting
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批准号:9895819
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项目类别:
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资助金额:$34.15万
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财政年份:2011
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负责人:Tobias C Walther
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依托单位:
Mechanisms of Lipid Droplet Protein Targeting
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批准号:8738798
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项目类别:
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资助金额:$6.32万
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财政年份:2011
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负责人:Tobias C Walther
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依托单位:
Mechanisms of Lipid Droplet Protein Targeting
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批准号:8725690
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项目类别:
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资助金额:$40.38万
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财政年份:2011
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负责人:Tobias C Walther
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依托单位:
Mechanisms of Lipid Droplet Protein Targeting
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批准号:10322126
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项目类别:
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资助金额:$29.89万
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财政年份:2011
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负责人:Tobias C Walther
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依托单位:
Mechanisms of Lipid Droplet Protein Targeting
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批准号:10704249
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项目类别:
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资助金额:$4.35万
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财政年份:2011
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负责人:Tobias C Walther
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依托单位:
Mechanisms of Lipid Droplet Protein Targeting
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批准号:10052146
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项目类别:
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资助金额:$31.9万
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财政年份:2011
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负责人:Tobias C Walther
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依托单位:
Mechanisms of Lipid Droplet Protein Targeting
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批准号:8339464
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项目类别:
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资助金额:$41.52万
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财政年份:2011
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负责人:Tobias C Walther
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依托单位:
Mechanisms of Lipid Droplet Protein Targeting
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批准号:8537217
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项目类别:
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资助金额:$40.17万
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财政年份:2011
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负责人:Tobias C Walther
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依托单位:
海外基金