Jl. Denburg et al., DEVELOPMENTAL-CHANGES IN EPITOPE ACCESSIBILITY AS AN INDICATOR OF MULTIPLE STATES OF AN IMMUNOGLOBULIN-LIKE NEURAL CELL-ADHESION MOLECULE, Journal of comparative neurology, 354(4), 1995, pp. 533-550
Cell surface molecules with restricted spatial and temporal distributi
ons are good candidates for mediators of the cell-cell interactions th
at are necessary for the development of the nervous system. A monoclon
al antibody (MAb 23A7) was produced that selectively and transiently l
abeled a limited subset of axons in the chick embryo spinal cord. Dete
rmination of the N-terminal amino acid sequence and immunoprecipitatio
n experiments demonstrated that the 23A7 antigen is identical to Bravo
/Nr-CAM, a previously described cell adhesion molecule with immunoglob
ulin-like domains (E.J. de la Rosa, J.F. Kayyem, J.M. Roman, Y.-D. Sti
erhof, 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 [1
991] J. Cell Biol. 113:1399-1412). The temporal distribution of the 23
A7 antigen is unusual in that, immunohistochemically, MAb 23A7 binding
greatly decreases after 7 days of development, whereas Western blot a
nalysis indicates increasing levels of the antigen until 17 days of de
velopment. In contrast, an antiserum against purified Nr-CAM, which al
so binds only to the 2387 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 sensitivit
y of the 23A7 epitope to fixation, the use of suboptimal concentration
s of the MAb, or selective MAb binding to a subset of Bravo/Nr-CAM mol
ecules produced by alternative splicing of the transcript or by posttr
anslational 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 sugg
ests the existence of multiple conformation or aggregation states of t
his cell adhesion molecule, each of which might be performing a differ
ent function. (C) 1995 Wiley-Liss, Inc.