Binding of Asymmetric (Al2) Acetylcholinesterase to C2 Muscle Cells and to Cho Mutants Defective in Glycosaminoglycan Synthesis

Abstract

The principal biological role of acetylcholinesterase (AChE) is termination of impulse transmission at cholinergie synapses by rapid hydrolysis of the neurotransmitter acetylcholine (Katz, 1966). AChE is a polymprphic enzyme which may be classified in globular and asymmetric forms (Bon et al., 1979). Of these, the tailed asymmetric Al2 form is found in high concentrations at endplates (Hall, 1973). The occurrence of a collagenous domain in the tailed enzyme suggests that it interacts with the extracellular matrix (Lwebuga-Mukasa et al., 1976; Inestrosa et al., 1982). It has been postulated that this interaction occurs through attachment to heparin-like glycosaminoglycans (GAGs) present in proteoglycans (PGs) (Brandan et al., 1985). In the present study we have directly evaluated the binding of purified Al2 AChE to cultured wild-type and mutant mouse C2 skeletal muscle cells. Also, to investigate the potential role of heparan sulfate proteoglycans (HSPGs) as Al2 AChE cell surface receptors, we studied the interactions of Al2 AChE with chinese hamster ovary (CHO) cells that synthesize varying amounts of cell surface heparan sulfate (HS) and other GAGs (Esko, 1991).