Targeting of proteins into peroxisomes

将蛋白质靶向过氧化物酶体

• 批准号: 8050526
• 负责人: Suresh Subramani
• 金额: $ 58.72万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-05-10 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8050526
• 关键词: Address; Affect; Back; Biochemical; Biogenesis; Biological; Biological Models; Cells; Complex; Cytosol; Disease; Docking; Eukaryotic Cell; Evolution; Genes; Growth; Health; Homeostasis; Human; Impairment; Instruction; Knowledge; Membrane Proteins; Metabolic; Morphogenesis; Nature; Organelles; Pathway interactions; Play; Positioning Attribute; Process; Protein Import; Protein translocation; Proteins; Role; Signal Transduction; Sorting - Cell Movement; Structure; Work; fascinate; lipid metabolism; peroxisome; peroxisome membrane; receptor; receptor binding; receptor recycling

The peroxisome, an essential subcellular compartment in all eukaryotic cells, is infimately involved in lipid metabolism. Work in multiple model systems has uncovered at least 32 PEX genes encoding peroxins, that play roles In peroxisome biogenesis, morphogenesis (size, volume and number), and inheritance. However, despite this wealth of knowledge regarding the proteins involved, the biochemical functions and mechanisms of acfion of most peroxins are pooriy understood. Peroxisomal proteins are targeted to the organelle matrix by two peroxisomal targefing signals, PTS1 and PTS2. PTS receptors bound to their cargo interact with the importomer, a complex of peroxisome-membrane-assoclated Pex proteins. The importomer, responsible for peroxisomal matrix protein translocation is comprised ofthe docking and RING subcomplexes. During the matrix protein import cycle, the receptor-cargo complexes shuttle from the cytosol, interact with the importomer, release cargo in the peroxisome matrix and the receptors then shutfie back to the cytosol, aided by a receptor-recycling subcomplex. Major unanswered questions in the peroxisome biogenesis field relate to the exact nature, function and structure ofthe unusual peroxisomal translocon which, unlike translocons associated with other subcellular compartments, transports folded and oligomeric proteins across (Aimi). The evolution of dual matrix protein import pathways and the steps in cargo release and receptor recycling from peroxisomes. Involving the function of Pex8, are critical for an understanding of the import cycle (Aim 2). The recent emergence of a clear involvement of the endoplasmic reficulum (ER) in peroxisome morphogenesis, and even biogenesis, raises important quesfions about the machinery that sorts peroxisomal membrane proteins via the ER and the funcfional role of this pathway in peroxisome growth and division (Aim 3). Finally, we wish to further explore fascinating emerging clues regarding a crosstalk between peroxisome biogenesis, inheritance and turnover (Aim 4). We believe we are uniquely positioned to answer these fundamentally important cell biological quesfions that seriously impact human health and disease. RELEVANCE (See instructions): Impairment of peroxisomal metabolic or biogenesis pathways causes 17, often fatal, human disorders. This proposal will address basic mechanisms involved in peroxisomal matrix and membrane protein assembly, growth and division. By doing so we hope to understand how organelle homeostasis is maintained and how the impairment of these processes can affect human health and disease.

过氧化物酶体是真核细胞中一个重要的亚细胞区室， 新陈代谢.在多个模型系统中的工作已经发现了至少32个编码过氧化物酶的PEX基因， 在过氧化物酶体生物发生、形态发生（大小、体积和数量）和遗传中发挥作用。然而，在这方面， 尽管关于所涉及的蛋白质、生物化学功能和 大多数过氧化物的作用机制尚不清楚。过氧化物酶体蛋白靶向于 细胞器基质的两个过氧化物酶体靶向信号，PTS 1和PTS 2。与其货物结合的PTS受体 相互作用的importomer，一个复杂的过氧化物酶体膜assoclated Pex蛋白。的 一种负责过氧化物酶体基质蛋白转运的重要分子，由对接和环组成 子复形在基质蛋白输入循环期间，受体-货物复合物从基质蛋白转运到受体。 与输入体相互作用，在过氧化物酶体基质中释放货物，然后受体关闭 在受体再循环亚复合物的帮助下，《公约》中未回答的主要问题 过氧化物酶体生物发生领域涉及到特殊过氧化物酶体的确切性质、功能和结构 与其他亚细胞区室相关的translocon不同，translocon运输折叠和 寡聚体蛋白（Aimi）。双基质蛋白输入途径的演变和步骤 过氧化物酶体的货物释放和受体再循环。涉及Pex 8的功能，对于一个 了解进口周期（目标2）。最近出现的一个明确的参与内质网 在过氧化物酶体形态发生，甚至生物发生中， 通过ER对过氧化物酶体膜蛋白进行分类的机制以及该途径在 过氧化物酶体的生长和分裂（Aim 3）。最后，我们希望进一步探索迷人的新兴线索， 关于过氧化物酶体生物发生、遗传和周转之间的串扰（Aim 4）。我们相信我们是 独特的定位来回答这些根本重要的细胞生物学问题， 人类健康和疾病。 相关性（参见说明）： 过氧化物酶体代谢或生物合成途径的损伤导致17种通常致命的人类疾病。这 提案将涉及过氧化物酶体基质和膜蛋白组装的基本机制， 成长与分裂通过这样做，我们希望了解细胞器内稳态是如何维持的，以及如何维持细胞内稳态的。 这些过程的损害可影响人类健康和疾病。