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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020728-05
Application #
3401285
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1984-04-01
Project End
1990-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92037
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Lai, C; Brow, M A; Nave, K A et al. (1987) Two forms of 1B236/myelin-associated glycoprotein, a cell adhesion molecule for postnatal neural development, are produced by alternative splicing. Proc Natl Acad Sci U S A 84:4337-41
Lai, C; Watson, J B; Bloom, F E et al. (1987) Neural protein 1B236/myelin-associated glycoprotein (MAG) defines a subgroup of the immunoglobulin superfamily. Immunol Rev 100:129-51
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Lenoir, D; Battenberg, E; Kiel, M et al. (1986) The brain-specific gene 1B236 is expressed postnatally in the developing rat brain. J Neurosci 6:522-30
Milner, R J; Lai, C; Lenoir, D et al. (1986) Brain-specific gene expression. Biochem Soc Symp 52:107-17
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Bloom, F E; Battenberg, E L; Milner, R J et al. (1985) Immunocytochemical mapping of 1B236, a brain-specific neuronal polypeptide deduced from the sequence of a cloned mRNA. J Neurosci 5:1781-802

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