PM-ER Membrane Contact Sites: Regulatory Interfaces for Cell Polarization and Membrane Signalling

PM-ER 膜接触位点：细胞极化和膜信号传导的调节接口

• 批准号: RGPIN-2016-03976
• 负责人: Beh, Christopher
• 金额: $ 3.21万
• 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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761189
• 关键词: PM; ER; Membrane; Contact; Sites

Cell growth is dictated in large part by the bustling traffic of molecular cargo moving between different membranes within cells. Fats and lipids are perhaps the most difficult cargo to transport. Like oil on water, fats and lipids do not mix well with the cell's internal fluid and require specialized transport systems to move around. Cholesterol transport represents a good example of this complication. Cholesterol is made within internal membranes and must be transferred to the cell surface, but how it moves is not well understood. Some evidence points to carrier proteins that shuttle cholesterol back-and-forth between membranes, but other results suggest that cholesterol is transferred at sites where different membranes come into direct contact with one another. We are testing these alternatives mechanisms as well as the possibility that both work together in parallel. These basic transport mechanisms operate in yeast as well as humans, so we have chosen to exploit the advantages of yeast molecular genetic techniques for cell manipulation. Yeast cells represent simple versions of our own cells, so what we learn in yeast can be applied to understanding transport within human cells. As we were conducting our studies we were surprised to find that membrane contact sites also have unanticipated roles in cell division. So, in addition to our goal of understanding all modes of lipid and membrane transport within cells, we intend to discover how membrane contact sites affects other aspects of cell growth and division.

细胞生长在很大程度上取决于细胞内不同膜之间分子货物的繁忙运输。脂肪和脂类可能是最难运输的货物。就像水上的油一样，脂肪和脂质不能很好地与细胞内部的液体混合，需要专门的运输系统才能四处移动。胆固醇转运是这种并发症的一个很好的例子。胆固醇是在细胞内膜内产生的，必须转移到细胞表面，但它是如何移动的还不清楚。一些证据表明，载体蛋白在膜之间来回穿梭胆固醇，但其他结果表明，胆固醇在不同膜相互直接接触的部位转移。我们正在测试这些替代机制以及两者并行工作的可能性。这些基本的运输机制在酵母和人类中运作，因此我们选择利用酵母分子遗传技术的优势进行细胞操作。酵母细胞代表了我们自己细胞的简单版本，因此我们在酵母中学到的东西可以应用于理解人类细胞内的运输。当我们进行研究时，我们惊讶地发现膜接触位点在细胞分裂中也有意想不到的作用。 因此，除了了解细胞内脂质和膜运输的所有模式外，我们还打算发现膜接触部位如何影响细胞生长和分裂的其他方面。