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

细胞的生长在很大程度上是由细胞内不同膜之间分子货物的繁忙交通所决定的。脂肪和脂质可能是最难运输的货物。就像油在水上一样，脂肪和脂类不能很好地与细胞内部的液体混合，需要专门的运输系统来移动。胆固醇转运就是这种并发症的一个很好的例子。胆固醇是在细胞膜内产生的，必须转移到细胞表面，但它是如何移动的还不清楚。一些证据指出，载体蛋白在细胞膜之间来回运送胆固醇，但其他结果表明，胆固醇是在不同细胞膜之间直接接触的地方转移的。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身细胞的简单版本，所以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，除了我们的目标是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。**

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. **