The adhesion function on acetylcholinesterase is located at the peripheral anionic site.
There is accumulating evidence that acetylcholinesterase has secondary noncholinergic functions, related to adhesion, differentiation, and the deposition of beta-amyloid in Alzheimer's disease. We have observed that the specific acetylcholinesterase peripheral anionic site inhibitors, BW284c51 and propidium iodide, abrogated cell-substrate adhesion in three human neuroblastoma cell lines. The active-site inhibitors, eserine and edrophonium, in contrast, had no effect. Certain anti-AChE antibodies were also shown to inhibit adhesion. Of these, the most effective were a monoclonal (E8) and a polyclonal having cholinesterase-like catalytic activity. These were raised against 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 antibodies have been shown to overlap the peripheral anionic site of acetylcholinesterase. Competition ELISA between the monoclonal antibodies and inhibitors indicated competition between E8, E62A1, and E65E8 and the peripheral-site inhibitors BW284c51 and propidium, but not with the active-site inhibitors eserine and edrophonium. Fluorescence titration between antibodies and propidium confirmed these results. We conclude that the adhesion function of acetylcholinesterase is located at the peripheral anionic site. This has implications, not only for our understanding of neural development and its disorders, but also for the treatment of neuroblastoma, the leukemias, and Alzheimer's disease.
D000110:Acetylcholinesterase / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D000838:Anions; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001667:Binding, Competitive; D002448:Cell Adhesion / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D006801:Humans; D015335:Molecular Probes; D011419:Propidium / Q000737:chemistry; D014407:Tumor Cells, Cultured