Peripheral Nervous System (PNS) myelin is a differentiated form of Schwann cell plasma membrane rich in glycoproteins. These glycoproteins may be crucial for myelin formation and maintenance, and may play a prominant role in the pathogenesis of acquired demyelinative neuropathies. The overall thrust of this proposal is to define and describe certain of these glycoproteins, and, as such, the investigation follows two avenues of approach: I) the detailed characterization of a newly recognized abundant PNS myelin glycoprotein (170,000 Mr) and II) the selection of certain potentially important PNS myelin glycoproteins from those many that yet remain undescribed. These will become candidates for more intensive study. I. The characterization of the newly recognized and apparently PNS myelin-specific 170,000 Mr glycoprotein will focus on defining its protein and carbohydrate proportions and on the analysis of its carbohydrate constituents. Polyclonal and monoclonal antibodies directed against this glycoprotein will be raised in order to prove PNS myelin specificity and to localize it within the myelin array. Studies designed to probe its metabolism will also employ these antibodies. Of particular interest in this regard are: 1) the precursor-product relations of the 170,000 Mr glycoprotein and 2) the potential induction of 170,000 Mr in cultured Schwann cells which have been exposed to axolemmal fragments or agents which raise intracellular cyclic adenosine 3',5'-monophosphate (cAMP) as examined by metabolic radiolabeling, immunoblot and immunocytochemical methods. II. This group of studies will facilitate recognition of PNS myelin glycoproteins with functional or disease-related significance and which thereby warrant more intensive characterization. The search is designed to identify: 1) glycoproteins pertinent to axon-Schwann cell interaction, and 2) the induction of glycoprotein synthesis by cultured Schwann cells exposed to agents which raise intracellular cAMP.
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