Sterol transport and cell-cycle requirements for isoprenoids

类异戊二烯的甾醇运输和细胞周期要求

• 批准号: 250263-2011
• 负责人: Beh, Christopher
• 金额: $ 2.62万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=506093
• 关键词: Sterol; transport; cell; cycle; requirements

Cholesterol is a necessary evil. Too much cholesterol leads to disease, but some cholesterol is nonetheless needed for normal cell growth. Cholesterol and related lipids are required for the structure of the membrane that envelopes cells, and cholesterol affects the function of proteins embedded within this membrane. In addition to the transport mechanisms that move cholesterol through our bodies, cholesterol must also be transported within the cell interior. The mechanism for how cholesterol moves within cells is poorly understood. OSBP-related proteins (ORPs) are implicated in the transport of cholesterol within cells, but how these proteins might accomplish that function is controversial. We have chosen to study ORPs and the transport of cholesterol-related sterols in yeast cells, which can be easily exploited using a large variety of molecular genetic techniques. Yeast also represent simple versions of our own cells, so what we learn in yeast can be applied to studies of cholesterol transport in human cells. The goal of our work is to define how cholesterol is transported within cells, and to understand how cholesterol and its biosynthetic precursors affect cell growth and division.

胆固醇是一种必要的邪恶。过多的胆固醇会导致疾病，但一些胆固醇仍然是正常细胞生长所必需的。胆固醇和相关脂质是包裹细胞的膜结构所必需的，并且胆固醇影响嵌入该膜内的蛋白质的功能。除了胆固醇在体内的运输机制外，胆固醇还必须在细胞内部运输。胆固醇如何在细胞内移动的机制知之甚少。OSBP相关蛋白（ORP）与细胞内胆固醇的转运有关，但这些蛋白如何实现这一功能仍有争议。我们选择研究ORP和酵母细胞中胆固醇相关甾醇的运输，这可以很容易地利用各种分子遗传技术。酵母也代表了我们自己细胞的简单版本，因此我们在酵母中所了解的可以应用于人体细胞中胆固醇运输的研究。我们工作的目标是确定胆固醇如何在细胞内运输，并了解胆固醇及其生物合成前体如何影响细胞生长和分裂。