NOVEL NERVOUS SYSTEM GLYCOPROTEINS IN AXONAL GROWTH

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The objectives are to understand the molecular mechanisms underlying axonal outgrowth. It is generally believed that molecules on the surface of growing axons interact with other molecules in their environment, and that these molecular interactions are essential for the achievement of normal neuronal connections. In our laboratory, a monoclonal antibody 4D7 has recently been prepared which recognizes a group of glycoproteins that are apparently involved in axonal growth. We propose a comprehensive group of studies of these 4D7 glycoproteins which are designed to answer the relationship between their structures and their functions. These studies include: 1) chemistry of the carbohydrate and peptide portions of the molecules. 2) analysis of the regulation of expression of these glycoproteins, and their relationship to previously described cell adhesion molecules, and 3) a study of the functional properties of these proteins, particularly their role in neurite outgrowth and axon regeneration. Analysis of these glycoproteins in the development of the mammalian nervous system may help us to understand the mechanisms of axonal growth in development of normal human brain. Any abnormalities in the expression of these proteins would likely have severe developmental consequences. Therefore, it is likely that this project will provide relevant information for future studies in mental retardation. And will also contribute to our knowledge of nerve regeneration, which could have positive implications for future treatment of peripheral nerve injuries. A multi-faceted approach is proposed for the analysis of these novel glycoproteins. The use of immunological and cell culture methods dominate these projects. Monoclonal antibodies, which are available, will be used for immunoaffinity chromatographic purification of proteins. These antibodies will also be used extensively for immunocytochemical studies at the light and electron microscopic levels. The antibodies will be used in primary culture systems to elucidate the functional properties of the glycoproteins. In addition, the production of monoclonal antibodies specific for each 4D7-immunoreactive proteins is planned to provide additional probes to carry out these projects.