Molecular analysis of CD44 in cell adhesion and migration

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CD44 is a cell adhesion molecule expressed on many cells in your body. We are interested in its function on white blood cells, the cells of the immune system that fight infection and disease. The CD44 molecule helps white blood cells arrive at the site of infection, helps resolve inflammation and heal wounds, and is also involved in the migration of tumor cells resulting in tumor metastasis. It is our hypothesis that CD44 interacts with its binding partner, hyaluronan (HA) a sugar molecule that can attach to the cell wall. This interaction regulates immune cell function by aiding cell movement throughout the body. One set of immune cells, called T cells, circulate throughout the body looking for invaders that cause infection. Once they find them, they stop, receive signals from other cells to become armed, then migrate through the blood to infected tissues to fight infection. Knowing when to migrate and when to stop is critical to their function. In this study we will determine how the interaction of CD44 with HA influences T cell adhesion and mobility. When CD44 attaches to HA, signals are transmitted to a network of proteins inside the cell that change the cell's shape and cause mobility. Changes to this network are required each time the cell moves, thus signals that change this network can affect cell mobility. We have found that CD44 signals via an enzyme (catalyst) that is associated with CD44 inside the cell. We are now looking for substrates (targets) of this enzyme to follow the signaling pathway directly to the network using immunochemistry and biochemical techniques. We have found that HA signals through CD44 to destabilize the cell structure, thus allowing the network to remodel and the cell to change its shape. This basic research into what makes a cell stop or migrate is of fundamental importance in cell biology. Understanding at the molecular level what regulates immune cell adhesion and migration is an important step towards the future development of new biotechnologies designed to facilitate, mimic or prevent cell movement or cell adhesion. By investing in this basic research, Canadians are ensuring the continuation of scientific discovery and progress for future generations.