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Using Arabidopsis to uncover new roles for peroxins

利用拟南芥发现过氧化物酶的新作用

基本信息

批准号：
7776897
负责人：
Bonnie Bartel
金额：
$ 28.58万
依托单位：
RICE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-03-01 至 2013-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7776897
关键词：
26S proteasome Address Amino Acid Sequence Arabidopsis Biogenesis Biological Assay Biology Candidate Disease Gene Cell Fractionation Cells Chimeric Proteins Craniofacial Abnormalities Cytosol Data Defect Development Disease Dissection Eukaryota Excision Exhibits Fluorescence Fluorescence Microscopy Fractionation Genes Genetic Germination Glyoxysomes Housing Human Human Development Hydrogen Peroxide Immunoblotting Immunofluorescence Microscopy Inherited Isocitrate Lyase Knowledge Malate Synthase Mental Retardation Metabolic Modeling Modification Molecular Monitor Mouse-ear Cress Mutation Neurons Organelles Organism PXR1 protein Plants Play Process Protein Import Proteins Reaction Recycling Reporter Research Role Seedling Signal Transduction Staging Symptoms Syndrome System Systems Biology Testing Variant Work base gene discovery infancy insight migration model development molecular marker multicatalytic endopeptidase complex mutant novel peroxisome plant growth/development protein degradation public health relevance receptor receptor recycling research study

项目摘要

DESCRIPTION (provided by applicant): Peroxisomes are metabolic compartments that are essential for human and plant development. Although understanding of how matrix proteins are imported into peroxisomes is increasing, mechanisms for turning over damaged or obsolete peroxisomal proteins remain largely obscure. The proposed studies will address peroxisome-associated protein degradation in Arabidopsis thaliana; the unique peroxisomal functions and facile genetics of this system will allow dissection of peroxisomal processes in an intact organism. Peroxins, encoded by PEX genes, are necessary for peroxisome biogenesis. Most peroxins act in matrix protein import; this work will determine whether a subset of these peroxins have additional roles in matrix protein turnover. Preliminary data suggest that a subset of peroxins work together both in receptor recycling and in a novel type of retrotranslocation - the removal for degradation of peroxisomal matrix proteins that are damaged or no longer needed. Three specific aims are proposed to identify components and molecular requirements of peroxisome-associated protein degradation. Aim 1 will characterize matrix protein localization and stability in mutants defective in peroxins and proteasome subunits. Aim 2 will identify cis-acting molecular signals necessary for degradation of two peroxisomal matrix proteins that undergo regulated destruction during a specific stage of seedling development. Aim 3 will recover mutants defective in known and undiscovered components of the peroxisome-associated degradation machinery. The successful completion of these aims will begin to address an unsolved mystery of peroxisome biology: How do peroxisomes dispose of damaged or obsolete proteins? Peroxisomal defects underlie a group of inherited syndromes known as peroxisome biogenesis disorders, which are generally fatal in infancy and are characterized by severe mental retardation, neuronal migration defects, craniofacial abnormalities, and other symptoms. The proposed experiments will exploit unique aspects of plant peroxisomes while taking advantage of knowledge from fungal and mammalian systems to provide insights that are likely to apply throughout eukaryotes. Adding an evolutionarily distinct model to the study of peroxisome biology will allow the development of model and hypotheses to expand and refine our understanding of these essential organelles. PUBLIC HEALTH RELEVANCE: Using Arabidopsis to Uncover New Roles for Peroxins Peroxisomes are subcellular compartments housing critical metabolic reactions and are essential for normal human development. Peroxisomal defects underlie a group of inherited syndromes known as peroxisome biogenesis disorders, which are generally fatal early in infancy. The proposed experiments will elucidate how cells dispose of proteins within peroxisomes when they are damaged or no longer needed.

描述（由申请人提供）：过氧化物酶体是人类和植物发育所必需的代谢区室。虽然对基质蛋白如何进入过氧化物酶体的理解越来越多，但修复受损或废弃的过氧化物酶体蛋白的机制仍然很不清楚。拟议的研究将解决过氧化物酶体相关的蛋白质降解拟南芥，独特的过氧化物酶体功能和该系统的简单遗传学将允许解剖过氧化物酶体过程中的一个完整的有机体。PEX基因编码的过氧化物酶是过氧化物酶体生物合成所必需的。大多数过氧化物酶在基质蛋白的进口行为，这项工作将确定这些过氧化物酶的子集是否有额外的作用，在基质蛋白的营业额。初步数据表明，过氧化物酶的一个子集在受体回收和一种新类型的逆转录-去除受损或不再需要的过氧化物酶体基质蛋白的降解中一起工作。提出了三个具体的目标，以确定过氧化物酶体相关蛋白降解的组分和分子要求。目的1将在过氧化物酶和蛋白酶体亚基缺陷的突变体中表征基质蛋白的定位和稳定性。目的2将确定在幼苗发育的特定阶段进行调节破坏的两个过氧化物酶体基质蛋白降解所需的顺式作用分子信号。目标3将恢复突变体缺陷的过氧化物酶体相关的降解机制的已知和未发现的组件。这些目标的成功完成将开始解决过氧化物酶体生物学的一个未解之谜：过氧化物酶体如何处理受损或废弃的蛋白质？过氧化物酶体缺陷是一组称为过氧化物酶体生物发生障碍的遗传综合征的基础，其通常在婴儿期是致命的，并且特征在于严重的智力迟钝、神经元迁移缺陷、颅面异常和其他症状。拟议的实验将利用植物过氧化物酶体的独特方面，同时利用真菌和哺乳动物系统的知识，提供可能适用于整个真核生物的见解。在过氧化物酶体生物学的研究中加入一个进化上独特的模型将允许模型和假设的发展，以扩展和完善我们对这些基本细胞器的理解。公共卫生相关性：利用拟南芥揭示过氧化物酶的新作用过氧化物酶体是容纳关键代谢反应的亚细胞区室，对人类正常发育至关重要。过氧化物酶体缺陷是一组称为过氧化物酶体生物发生障碍的遗传综合征的基础，这些遗传综合征通常在婴儿早期是致命的。拟议的实验将阐明细胞如何处理过氧化物酶体内的蛋白质时，他们被损坏或不再需要。