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: 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
• 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

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）：过氧化物酶体是对人类和植物发育至关重要的代谢室。尽管了解如何将基质蛋白进口到过氧化物酶体中的情况正在增加，但转移受损或过时的过氧化物酶体蛋白的机制仍然很大程度上晦涩。拟议的研究将解决拟南芥中与过氧化物酶体相关的蛋白质降解；该系统的独特的过氧化物酶体功能和便捷遗传学将使完整生物的过氧化物酶体过程解剖。通过PEX基因编码的过氧蛋白对于过氧化物酶体生物发生是必需的。大多数过氧素在基质蛋白进口中起作用；这项工作将确定这些过氧蛋白的子集是否在基质蛋白周转率中具有其他作用。初步数据表明，过氧蛋白的子集在受体回收和新型的逆转录旋转类型中共同起作用 - 去除过氧化物酶体基质蛋白的去除，这些蛋白被损坏或不再需要。提出了三个特定的目的，以确定过氧化物酶体相关蛋白降解的成分和分子需求。 AIM 1将表征过氧蛋白和蛋白酶体亚基中有缺陷的突变体中的基质蛋白定位和稳定性。 AIM 2将确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，这些蛋白会在幼苗发育的特定阶段受到调节的破坏。 AIM 3将恢复过氧化物酶体相关降解机制的已知和未发现组件中有缺陷的突变体。这些目标的成功完成将开始解决未解决的过氧化物酶体生物学的奥秘：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称为过氧化物酶体生物发生疾病的遗传综合征，这些综合症通常在婴儿期致命，其特征是严重的智力低下，神经元迁移缺陷，颅骨异常异常和其他症状。提出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在整个真核生物中适用的见解。在过氧化物酶体生物学的研究中添加进化不同的模型将使模型和假设的发展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：使用拟南芥来揭示过氧化物酶体的新作用是壳体的亚细胞隔室，其壳体的代谢反应至关重要，对于正常的人类发展至关重要。过氧化物酶体缺陷是一组称为过氧化物酶体生物发生疾病的遗传综合征，这些综合症通常是婴儿期的致命性。提出的实验将阐明细胞在受损或不再需要时如何处置过氧化物酶体内的蛋白质。