Developmental changes in epitope accessibility as an indicator of multiple states of an immunoglobulin-like neural cell adhesion molecule.
Cell surface molecules with restricted spatial and temporal distributions are good candidates for mediators of the cell-cell interactions that are necessary for the development of the nervous system. A monoclonal antibody (MAb 23A7) was produced that selectively and transiently labeled a limited subset of axons in the chick embryo spinal cord. Determination of the N-terminal amino acid sequence and immunoprecipitation experiments demonstrated that the 23A7 antigen is identical to Bravo/ Nr-CAM, a previously described cell adhesion molecule with immunoglobulin-like domains (E.J. de la Rosa, J.F. Kayyem, J.M. Roman, Y.-D. Stierhof, W.J. Dreyer, and U. Schwartz [1989] J. Cell Biol. 111:3087-3096; M. Grumet, V. Mauro, M.P. Goon, G.M. Edelman, and B.A. Cunningham [1991] J. Cell Biol. 113:1399-1412). The temporal distribution of the 23A7 antigen is unusual in that, immunohistochemically, MAb 23A7 binding greatly decreases after 7 days of development, whereas Western blot analysis indicates increasing levels of the antigen until 17 days of development. In contrast, an antiserum against purified Nr-CAM, which also binds only to the 23A7 antigen, labels nearly all the axons in the tissue throughout all the later stages of development. These anomalous observations are apparently not the result of differential sensitivity of the 23A7 epitope to fixation, the use of suboptimal concentrations of the MAb, or selective MAb binding to a subset of Bravo/ Nr-CAM molecules produced by alternative splicing of the transcript or by posttranslational modification. These findings could indicate the existence of multiple states of Bravo/ Nr-CAM, which during development, vary in the accessibility of their extracellular domains to the MAb. This suggests the existence of multiple conformation or aggregation states of this cell adhesion molecule, each of which might be performing a different function.[1]References
- Developmental changes in epitope accessibility as an indicator of multiple states of an immunoglobulin-like neural cell adhesion molecule. Denburg, J.L., Caldwell, R.T., Marner, J.M. J. Comp. Neurol. (1995) [Pubmed]
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