Cell-cell adhesion plays a central role in a variety of developmental events, particularly in the establishment of the nervous system. Moreover, recent studies indicate that alterations in the expression of cell adhesion molecules (CAMs) accompany a number of pathological states. Since our five segments resembling the structural domains of immunoglobulin and two other segments that are similar to regions (type III repeats) of the substrate other cell adhesion molecules, particularly in the nervous systems of both vertebrates and insects. Chicken neuron-glia cell adhesion molecule, Ng- CAM, and its murine homologue, the L1 antigen have six immunoglobulin-like domains and four fibronectin type III repeats. Ng-CAM mediates neuron-glia adhesion and neuron-neuron adhesion and is especially important in neurite fasciculation. In characterizing Ng-CAM, we also identified chicken cDNA clones that encode a novel protein very similar to Ng-CAM. This neural adhesion related (Nar)-molecule is apparently expressed on neurons and probably mediates adhesion between neurons or between neurons and glia. We propose to characterize the structure and function of this molecule with the aim of establishing whether it plays a role in such critical processes as neurite outgrowth, neurite fasciculation, nerve guidance, and neuron-glia interactions. The Nar-molecule resembles Ng-CAM (and L1) more closely than it does N-CAM or any other neural molecule, suggesting that the Nar- molecule and Ng-CAM are part of a subfamily of neural cell adhesion molecules. Using conserved sequences from these molecules we will construct probes to isolate and characterize other such molecules we will construct probes to isolate and characterize other such molecules by low stringency DNA hybridization and polymerase chain reaction techniques. Characterization of new neural CAMs and the development of antibody and DNA probes for each could have an important impact on the diagnosis of neuronal disorders and degenerative diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS028932-01
Application #
3415643
Study Section
Neurology C Study Section (NEUC)
Project Start
1990-08-01
Project End
1993-07-31
Budget Start
1990-08-01
Budget End
1991-07-31
Support Year
1
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Rockefeller University
Department
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Cunningham, B A (1995) Cell adhesion molecules as morphoregulators. Curr Opin Cell Biol 7:628-33
Krushel, L A; Prieto, A L; Cunningham, B A et al. (1993) Expression patterns of the cell adhesion molecule Nr-CAM during histogenesis of the chick nervous system. Neuroscience 53:797-812
Mauro, V P; Krushel, L A; Cunningham, B A et al. (1992) Homophilic and heterophilic binding activities of Nr-CAM, a nervous system cell adhesion molecule. J Cell Biol 119:191-202
Grumet, M; Mauro, V; Burgoon, M P et al. (1991) Structure of a new nervous system glycoprotein, Nr-CAM, and its relationship to subgroups of neural cell adhesion molecules. J Cell Biol 113:1399-412