The adhesion function on acetylcholinesterase is located at the peripheralanionic site

There is accumulating evidence that acetylcholinesterase has secondary nonc holinergic functions, related to adhesion, differentiation, and the deposit ion of beta-amyloid in Alzheimer's disease. We have observed that the speci fic acetylcholinesterase peripheral anionic site inhibitors, BW284c51 and p ropidium iodide, abrogated cell-substrate adhesion in three human neuroblas toma cell lines. The active-site inhibitors, eserine and edrophonium, in co ntrast, had no effect. Certain anti-AChE antibodies were also shown to inhi bit adhesion. Of these, the most effective were a monoclonal (E8) and a pol yclonal having cholinesterase-like catalytic activity. These were raised ag ainst an acetylcholinesterase-inhibitor complex, implying that the epitope is associated with active-site structures. Two other monoclonal antibodies (E62A1 and E65E8) partially inhibited adhesion. The epitopes of these antib odies have been shown to overlap the peripheral anionic site of acetylcholi nesterase. Competition ELISA between the monoclonal antibodies and inhibito rs indicated competition between E8, E62A1, and E65E8 and the peripheral-si te inhibitors BW284c51 and propidium, but not with the active-site inhibito rs eserine and edrophonium. Fluorescence titration between antibodies and p ropidium confirmed these results. We conclude that the adhesion function of acetylcholinesterase is located at the peripheral anionic site. This has i mplications, not only for our understanding of neural development and its d isorders, but also for the treatment of neuroblastoma, the leukemias, and A lzheimer's disease. (C) 1999 Academic Press.