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

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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. **