title: Distinct localization of collagen Q and PRiMA forms of acetylcholinesterase at the neuromuscular junction.
abstract: Acetylcholinesterase (AChE) terminates the action of acetylcholine at cholinergic synapses thereby preventing rebinding of acetylcholine to nicotinic postsynaptic receptors at the neuromuscular junction. Here we show that AChE is not localized close to these receptors on the postsynaptic surface, but is instead clustered along the presynaptic membrane and deep in the postsynaptic folds. Because AChE is anchored by ColQ in the basal lamina and is linked to the plasma membrane by a transmembrane subunit (PRiMA), we used a genetic approach to evaluate the respective contribution of each anchoring oligomer. By visualization and quantification of AChE in mouse strains devoid of ColQ, PRiMA or AChE, specifically in the muscle, we found that along the nerve terminus the vast majority of AChE is anchored by ColQ that is only produced by the muscle, whereas very minor amounts of AChE are anchored by PRiMA that is produced by motoneurons. In its synaptic location, AChE is therefore positioned to scavenge ACh that effluxes from the nerve by non-quantal release. AChE-PRiMA, produced by the muscle, is diffusely distributed along the muscle in extrajunctional regions.
authors.affiliation: Université Paris Descartes, 45 rue des Saints Pères, 75006 Paris, France. veronique.bernard@snv.jussieu.fr
authors.forename: Véronique
authors.initials: V
authors.lastname: Bernard
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Girard
authors.forename: Anna
authors.initials: A
authors.lastname: Hrabovska
authors.forename: Shelley
authors.initials: S
authors.lastname: Camp
authors.forename: Palmer
authors.initials: P
authors.lastname: Taylor
authors.forename: Benoit
authors.initials: B
authors.lastname: Plaud
authors.forename: Eric
authors.initials: E
authors.lastname: Krejci
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism* / Q000648:ultrastructure; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D002038:Bungarotoxins; D007527:Isoenzymes; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C486718:prima1 protein, mouse; D003094:Collagen; D000110:Acetylcholinesterase; D000109:Acetylcholine