Unconventional ER exit pathway in mammalian Cells

哺乳动物细胞中非常规的 ER 退出途径

• 批准号: RGPIN-2015-04077
• 负责人: Kim, Peter
• 金额: $ 2.77万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=687239
• 关键词: Unconventional; ER; exit; pathway; mammalian; Unconventional; ER; exit; pathway; mammalian

A hallmark of eukaryotic cells is the diverse array of subcellular organelles that compartmentalize the various biochemical reactions essential to life. These cells have developed elegant cellular processes to form and maintain the various organelles based on the needs of the cell. One such process is the correct targeting of proteins to their designated organelle to allow for the specialized functions of the organelle. A defect in protein targeting can lead to failure of critical cellular processes leading to cell death and/or disease. My research group is interested in understanding the mechanisms through which proteins exit the endoplasmic reticulum (ER) to various organelles. One such organelle is the peroxisome. This small organelle houses enzymes, which are involved in a wide variety of biological reactions that are critical for the survival of the organism. Yet, a basic understanding how peroxisomes are formed is still lacking. We have recently shown that peroxisomes receive some of their membrane proteins from the ER. This export of protein from ER to peroxisomes is independent of conventional protein exit pathways. Therefore, the overall goal of our research proposal is to understand the basic mechanism(s) by which proteins are transport from the ER to peroxisome in mammalian cells. We will address this using state-of-the-art imaging technology coupled with genetics and biochemical techniques. These studies will have broad contextual importance since peroxisome function is conserved between multi-cellular organisms, like plants, where peroxisomes play a critical role in their growth. Ultimately, the findings through this research will not only further our understanding of peroxisome formation from the ER but also the innovative techniques developed through these studies can also be utilized to examine other topics of cell biology. Moreover, it will provide training in cutting-edge microscopy techniques to developing young scientists who will be well prepared for successful careers in Canadian academia, government, and industry.**

真核细胞的标志是一系列不同的亚细胞细胞器，它们会使生命必不可少的各种生化反应划分。这些细胞开发出优雅的细胞过程，以根据细胞的需求形成和维护各种细胞器。这样的过程之一就是将蛋白质正确靶向其指定的细胞器，以允许细胞器的专门功能。蛋白质靶向的缺陷会导致关键细胞过程失败，导致细胞死亡和/或疾病。我的研究小组有兴趣了解蛋白质将内质网（ER）退出到各种细胞器的机制。一个这样的细胞器就是过氧组合体。这个小小的细胞器构成了酶，这些酶参与了各种对组织生存至关重要的生物反应。然而，仍然缺乏基本了解过氧化物体的形成。我们最近表明，过氧化物体从ER接收一些膜蛋白。这种从ER到过氧化物体的蛋白质导出与常规蛋白质出口途径无关。因此，我们的研究建议的总体目标是了解蛋白质在哺乳动物细胞中从ER转移到过氧化物体的基本机制。我们将使用最先进的成像技术以及遗传学和生化技术来解决此问题。这些研究将具有广泛的上下文重要性，因为在多细胞生物（如植物）之间保守了过氧化物，过氧化物体在其生长中起着至关重要的作用。最终，通过这项研究的发现不仅将进一步了解来自ER的过氧化物体形成，而且还可以利用通过这些研究开发的创新技术来研究细胞生物学的其他主题。此外，它将为正在发展的年轻科学家提供尖端显微镜技术的培训，这些科学家将为在加拿大学术界，政府和行业的成功职业做好准备。**