The recruitment of cytoplasmic signaling proteins provides an intracellular cue to modulate adhesive properties of the synapse (inside-out signaling) ( Figure 1) and to propagate broader changes in cell structure and function. In some instances, a synapse may establish cell polarity in a different cell axis (e.g., the apicobasal axis) ( Figure 1). Homophilic adhesion potentially recruits the same cytoplasmic signaling proteins to opposing membranes to generate a symmetric synapse, unless different sets of binding proteins were expressed in each of the opposing cells, resulting in an asymmetric synapse. Heterophilic adhesion on opposing cells potentially recruits different cytoplasmic signaling proteins to each membrane to generate structural and functional asymmetry at the synapse.
Because proper cell organizations arise from these specific cell interactions, cell adhesion proteins likely play instructive roles in promoting local specifications of the synapse that impact overall cellular functions (outside-in signaling) ( Figure 1). Sherrington and his colleagues used “synapse” to describe adhesions between neurons, although the etymology of the word implies a more general cellular context as discussed here.Ĭorrect interactions between cells to form synapses require cell-cell recognition by adhesion proteins, which leads to cell sorting as some cells adhere to each other and others are excluded. In specialized cell contexts, cell-cell adhesion is synonymous with a “synapse,” a word coined in 1897 by the English physiologist and 1932 Nobel Laureate Sir Charles Sherrington from the Greek word “ sunaptein” meaning to fasten together (“ sun-” together, and “ haptein” to fasten or bind) (for a historical perspective, and quotes see Reference 1). In the adult, cell-cell adhesion not only maintains the structural and functional integrity of those organs and tissues, but it must be sufficiently dynamic to allow the formation of new cell interactions and the remodeling of old ones. During development, specific adhesion between distinct cell types is required for the correct organization of cells into patterns that give rise to different organs and tissues. Cell-cell adhesion is a fundamental characteristic of multicellular organisms.
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