In developing neural systems, cell-cell contact is important for what are generally considered as mechanical processes, such as the pathfinding of growing neurites. Cell adhesion molecules are thus thought of as passive """"""""glues"""""""" to hold cells together. However, recent studies show that cell-cell contact can also mediate changes in cellular biochemistry in the nervous system, such as changes in neurotransmitter biosynthetic enzymes. This proposal focusses on exploring the importance of cell adhesion molecules in mediating communication between cells, via production of biochemical signals. Our preliminary data indicate that choline acetyltransferase is regulated by cell-cell contact in chick sympathetic neurons. This effect can be mimicked by the addition of membranes to cells, and the effect of membranes can be blocked by the addition of Fab fragments directed against the neural cell adhesion molecules (NCAM). These data suggest two possible roles for NCAM in this phenomenon: involvement in agglutination of membranes to cells, allowing a different ligand-receptor interaction to function, or direct involvement in the signalling process itself. The experiments described in this proposal are designed to distinguish between these two possible roles, and to assess the contribution of other cell adhesion molecules to this phenomenon. The experiments include: (a) examination of the effects of altered NCAM function, which can be perturbed in two ways: enhancement of NCAM binding by endoneuraminidase N-mediated desialylation of the molecule, and inhibition of NCAM binding by anti-NCAM Fab fragments, (b) evaluation of the role played by axon-CAM, another cell adhesion molecule present on these cells, (c) exploration of the effect of purified cell adhesion molecules on cells, and (d) examination of the potential role of NCAM's cytoplasmic domain, which is phosphorylated, in an active signalling process. Information provided by these studies could generate a new concept about the role of cell adhesion in the development of the nervous system: an active means of communication between cells.
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