Using Arabidopsis to uncover new roles for peroxins

利用拟南芥发现过氧化物酶的新作用

• 批准号: 8215748
• 负责人: Bonnie Bartel
• 金额: $ 28.3万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8215748
• 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; Health; Housing; 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; 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; receptor; receptor recycling; research study

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。尽管对基质蛋白如何导入过氧化物酶体的了解不断增加，但翻转受损或过时的过氧化物酶体蛋白的机制仍然很大程度上不清楚。拟议的研究将解决拟南芥中过氧化物酶体相关的蛋白质降解问题；该系统独特的过氧化物酶体功能和简单的遗传学将允许解剖完整生物体中的过氧化物酶体过程。过氧化物酶由 PEX 基因编码，是过氧化物酶体生物发生所必需的。大多数过氧化物酶在基质蛋白输入中发挥作用；这项工作将确定这些过氧化物酶的一个子集是否在基质蛋白周转中具有额外的作用。初步数据表明，过氧化物酶的一个子集在受体再循环和新型逆转位中共同发挥作用，即去除受损或不再需要的过氧化物酶体基质蛋白以进行降解。提出了三个具体目标来确定过氧化物酶体相关蛋白质降解的成分和分子要求。目标 1 将表征过氧化物酶和蛋白酶体亚基缺陷突变体中的基质蛋白定位和稳定性。目标 2 将鉴定两种过氧化物酶体基质蛋白降解所需的顺式作用分子信号，这两种过氧化物酶体基质蛋白在幼苗发育的特定阶段经历受调节的破坏。目标 3 将恢复在过氧化物酶体相关降解机制的已知和未发现的组件中存在缺陷的突变体。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过时的蛋白质？过氧化物酶体缺陷是一组被称为过氧化物酶体生物发生障碍的遗传综合征的基础，这些综合征通常在婴儿期致命，其特征是严重智力低下、神经元迁移缺陷、颅面畸形和其他症状。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来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研究中添加一个进化上独特的模型将使模型和假设的发展能够扩大和完善我们对这些重要细胞器的理解。公共卫生相关性：利用拟南芥发现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，对于正常人类发育至关重要。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，这些综合征通常在婴儿早期致命。拟议的实验将阐明当过氧化物酶体内的蛋白质受损或不再需要时，细胞如何处理它们。