The rat brain protein 1B236 is a membrane-associated glycoprotein of approximately 100,000 daltons that was defined originally by molecular cloning of brain-enriched mRNAs. Previous studies have provided the complete amino acid sequence of 1B236 and have demonstrated several interesting features of this molecule: a) the amino terminal region consists of five, roughly equal-sized domains that are homologous to each other and to proteins of the immunoglobulin superfamily; b) peptide fragments of the carboxyl terminus, as well as the predominant 100,000 dalton form of the 1B236 protein, can be detected in brain extracts by antibodies against appropriate synthetic peptides; c) several forms of 1B236 mRNA are generated by differential exon splicing: one mRNA encodes a 1B236 protein with a variant carboxyl terminus; d) at 12-25 days after birth 1B236 and protein are expressed abundantly in oligodendrocytes, coincident with myelinogenesis, in contrast to the adult where 1B236 expression is largely neuronal; e) preliminary evidence suggests that the 1B236 protein is identical or very similar to the previously described protein, myelin associated glycoprotein. It is the aim of the proposed studies to: 1. Determine the relationship between myelin associated glycoprotein and the 1B236 molecules expressed in oligodendrocytes and neurons. 2. Investigate the expression in the brain of the differentially spliced forms of 1B236 mRNAs and their encoded proteins. 3. Determine the complete structure of the 1B236 gene and analyse its regulation. 4. Determine the subcellular localization of the 1B236 glycoprotein and peptide forms and investigate the mechanism of their biosynthesis. 5. Test for molecules that may interact with the 1B236 glycoprotein or peptides. 6. Search for related molecules expressed in the brains and other tissues of rates and other species. These studies will generate further structural and genetic information for the 1B236 protein, which may be identical to myelin associated glycoprotein. The data will provide the basis for functional testing of the 1B236 protein, which is expressed in a highly regulated fashion in particular subpopulations of both neurons and glia. The apparent involvement of the 1B236 protein in myelinogenesis suggest that the study of this molecule may also further our understanding of demyelinating diseases.
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