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, where 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 micro-environment. Other data indicate that these macromolecules are involved in the saltatory conduction of the nerve impulse, and in synaptic transmission at the levels of the synthesis storage and release of neurotransmitters. The present proposal represents a continuation of our studies on their structure, localization, metabolism and functional roles. We expect to devote the major part of our efforts to the following areas: 1.) Complex carbohydrates of nervous tissue storage organelles, including those present in chromaffin granules of the adrenal medulla, densecored noradrenergic vesicles of sympathetic nerve terminals and synaptic vesicles from brain. Particular attention will be devoted to the carbohydrate moiety of dopamine Beta-hydroxylase, and possible differences between the soluble and membrane-bound forms of this enzyme. 2.) Studies on the structure and localization of a well-characterized chondroitin sulfate proteoglycan from brain (where it may be partially present as an extracellular matrix material) using biochemical and immunocytochemical techniques. The heparan sulfate proteoglycan of brain will also be isolated and characterized. 3.) Developmental studies on the localization of hyaluronic acid and the fine structure of the heparan sulfate polysaccharide chains. 4.) The biosynthesis and structure of complex carbohydrates on the cell surface and in catecholamine storage vesicles of cultured pheochromocytoma cells and sympathetic neurons, both of which undergo characteristic changes in response to treatment with nerve growth factor.
