Functional analysis of posttranslational cleavage products of the neuron-glia cell adhesion molecule, Ng-CAM.
Open Access
- 1 August 1995
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 130 (3) , 733-744
- https://doi.org/10.1083/jcb.130.3.733
Abstract
Neuron-glia cell adhesion molecule (Ng-CAM) mediates cell adhesion between neurons homophilically and between neurons and glia heterophilically; it also promotes neurite outgrowth. In the chick brain, Ng-CAM is detected as glycoproteins of 190 and 210 kD (Ng-CAM200) with posttranslational cleavage products of 135 kD (F135, which contains most of the extracellular region) and 80 kD (F80, which includes the transmembrane and the cytoplasmic domains). To examine the functions of each of these components, we have expressed Ng-CAM200, F135, and F80 in murine L cells, and F135 and F80 as GST fusion proteins in the pGEX vector in bacteria. Appropriately transfected L cells expressed each of these proteins on their surfaces; F135 was also found in the media of cells transfected with Ng-CAM200 and F135. In addition to binding homophilically, cells transfected with Ng-CAM200 and F135 bound heterophilically to untransfected L cells, suggesting that there is a ligand for Ng-CAM on fibroblasts that may be related to the glial ligand. Detailed studies using the transfected cells and the fusion proteins indicated that both the homophilic and the heterophilic binding activities of Ng-CAM are localized in the F135 fragment of the molecule. The results also indicated that proteolytic cleavage of Ng-CAM200 is not required either for its expression on the cell surface or for cell adhesion and that there is an "anchor" for F135 on L cells (and presumably on neurons). In contrast to the cell binding results, the F80 but not the F135 fusion protein enhanced the outgrowth of neurites from dorsal root ganglion cells; this activity was associated with the FnIII repeats of F80. The observations that a protein corresponding to F135 contains the cell aggregation sites whereas one corresponding to the F80 has the ability to promote neurite outgrowth suggest that proteolytic cleavage may be an important event in regulating these Ng-CAM activities during embryonic development and neural regeneration.Keywords
This publication has 46 references indexed in Scilit:
- The axonal recognition molecule F11 is a multifunctional protein: Specific domains mediate interactions with Ng-CAM and restrictinNeuron, 1993
- Bravo/Nr-CAM is closely related to the cell adhesion molecules L1 and Ng-CAM and has a similar heterodimer structure.The Journal of cell biology, 1992
- Neurite outgrowth on immobilized axonin-1 is mediated by a heterophilic interaction with L1(G4).The Journal of cell biology, 1991
- Structure of the chicken neuron-glia cell adhesion molecule, Ng-CAM: origin of the polypeptides and relation to the Ig superfamily.The Journal of cell biology, 1991
- Neurite outgrowth promoting activity of G4 and its inhibition by monoclonal antibodiesJournal of Neuroscience Research, 1990
- Functional mapping of cytotactin: proteolytic fragments active in cell-substrate adhesion.The Journal of cell biology, 1988
- Altered expression of neuronal cell adhesion molecules induced by nerve injury and repair.The Journal of cell biology, 1986
- Differential contributions of Ng-CAM and N-CAM to cell adhesion in different neural regions.The Journal of cell biology, 1986
- Initial appearance and regional distribution of the neuron-glia cell adhesion molecule in the chick embryo.The Journal of cell biology, 1985
- Neuron-Glia Adhesion Is Inhibited by Antibodies to Neural DeterminantsScience, 1983