MCS · Mammalian Cell Surface Reorganization During Cell Division

Cell division is a fundamental process by which all living things propagate. The cell surface is the only part of the cell that communicates with its environment, and is thus of critical importance for tissue development, homeostasis and disease. Almost all aspects of the cell’s interior undergo dramatic reorganization by the entry into mitosis and these changes have been extensively studied. In contrast, very little is known about how the cell surface changes during cell division, though surface changes are likely to be important in metazoan tissues and cancers. To investigate the cell surface reorganization during cell division, I took advantage of the quantitative proteomics analysis of cell-cycle to evaluate the changes in the cell surface as cells progress through mitosis.The proposed research will focus on proteins that we identified in our proteomic analysis as strongly up regulated on the cell surface in mitosis. Because, i) such regulation is unprecedented, and its mechanism is unknown, ii) these are rare changes, suggesting a single unique mechanism, and iii) a cell-surface biomarker for mitotic arrest could be useful for improving anti-mitotic cancer chemotherapy. Investigation of mitosis dependent surface-exposed proteins will reveal novel biological regulation, for example how dividing cells loose adhesion and cell round up, and also how mitotic cells interact with the extracellular matrix and communicate with their neighbors in tissue. I identified two members of the protocadherin family that are enriched on the mammalian cell surface as cells move from interphase to mitosis. This proposal will examine the upstream cellular mechanisms that cause cell cycle dependent surface exposure as well as the downstream consequences at the cellular and tissue levels. Investigating the function and the molecular mechanism of protocadherin 1&7 proteins, which are largely unstudied, promise to shed new lights on cell division and cell migration.