The objective of this project is to provide a foundation of basic neurochemical data concerning glycosaminoglycans (mucopolysaccharides) and glycoproteins, and building on this knowledge, to better understand their functional roles in nervous tissue. There is evidence that complex carbohydrates are present as cell-surface components of neurons and glia, and as an extracellular ground substance in the central nervous system. At these locations they are probably involved in mediating various types of cell-cell interactions and may also regulate the movements of ions and other substances in the brain cell microenvironment. Other data indicate that these macromolecules are involved in the saltatory conduction of the nerve impulse by modulating ion movements at the nodes of Ranvier, and in synaptic transmission at the levels of the synthesis, storage and release of neurotransmitters. The axonal transport of complex carbohydrates also indicates that they are utilized in some capacity at nerve endings. The present proposal represents a continuation of our studies over the past twelve years on the structure, localization, metabolism and functional roles of these compounds. We expect to devote the major part of our efforts to the following areas: 1) the structural characterization of a brain proteoglycan, and its possible presence in synaptic vesicles and the extracellular space, using both biochemical and immunohistochemical techniques; 2) developmental changes in neural membrane glycoproteins and glycosaminoglycans (especially heparan sulfate); and 3) the biosynthesis and structure of complex carbohydrates on the cell surface and in neurotransmitter storage organelles of cultured pheochromocytoma cells and sympathetic neurons.
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