Vertebrates have evolved a unique mechanism for regulation of cell interactions in order to accommodate the molecular and functional complexity of the central nervous system. This mechanism utilizes a very large and abundant cell surface carbohydrate (polysialic acid or PSA, specifically attached to the neural cell adhesion molecule NCAM) to titrate the intimacy of membrane-membrane contacts. By interfering with membrane apposition, PSA expression is able to cause a global reduction in cell interactions and thereby create permissive conditions for changes in cell position and shape. During development of the nervous system, these permissive conditions are known to facilitate the migration of neuronal precursors, the guidance of axons to their targets, and the formation of appropriate synapses.
Recently our lab has focussed on the retention of PSA in certain regions of the brain known to exhibit physiological and/or structural plasticity. While the role of PSA in the adult brain is similar at the cellular level to that during development, the physiological context is of course very different. Those contexts have led to a series of projects in the lab dealing with: