Complex carbohydrates and complementary carbohydrate receptors on opposing cells may mediate neural cell interactions. The current application focuses on gangliosides, a major class of cell surface glycoconjugates in the central nervous system (CNS), as potential neural recognition molecules. High-affinity ganglioside conjugates were synthesized and used to identify a novel brain ganglioside receptor which may by involved in neural cell interactions. Purification and molecular characterization of this and related receptors will provide unprecedented molecular and immunological tools with which to probe the functions of gangliosides and related glycosphingolipids. Myelin-associated ganglioside receptor. A high-affinity, ganglioside- specific binding activity was recently identified on CNS myelin membranes. Its saccharide specificity and membrane distribution suggest that it may be involved in oligodendroglial-axonal recognition. The primary goal of the next grant period will be the isolation and molecular characterization of this binding activity. Various synthetic ganglioside conjugates have been prepared for use as high-affinity radioligands, affinity chromatography matrices, and photoaffinity probes. Molecular biological techniques will be used to determine the sequence of the myelin ganglioside receptor and to generate molecular and immunological tools with which to probe its distribution, developmental expression, and function. Synaptosomal ganglioside receptor. A second ganglioside-specific binding activity was found enriched on rat brain synaptosomes. Saccharide specificity and tissue/subcellular distribution studies of this second brain ganglioside receptor will be performed, leading to its purification and molecular characterization. Sulfoglucuronyl glycosphingolipids in peripheral nervous system (PNS) cell recognition. Schwann cells, the myelin forming cells of the PNS, were found to adhere specifically to purified sulfoglucuronyl glycolipids, anionic glycosphingolipids implicated in certain peripheral neuropathies. Receptors complementary to these lipids were detected on PNS membranes. They will be characterized for saccharide and tissue specificity, with the goal of purification, molecular characterization, and functional studies.
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