title: Interaction of acetylcholinesterase with neurexin-1β regulates glutamatergic synaptic stability in hippocampal neurons.
abstract: BACKGROUND
  Excess expression of acetylcholinesterase (AChE) in the cortex and hippocampus causes a decrease in the number of glutamatergic synapses and alters the expression of neurexin and neuroligin, trans-synaptic proteins that control synaptic stability. The molecular sequence and three-dimensional structure of AChE are homologous to the corresponding aspects of the ectodomain of neuroligin. This study investigated whether excess AChE interacts physically with neurexin to destabilize glutamatergic synapses.
  
  
  RESULTS
  The results showed that AChE clusters colocalized with neurexin assemblies in the neurites of hippocampal neurons and that AChE co-immunoprecipitated with neurexin from the lysate of these neurons. Moreover, when expressed in human embryonic kidney 293 cells, N-glycosylated AChE co-immunoprecipitated with non-O-glycosylated neurexin-1β, with N-glycosylation of the AChE being required for this co-precipitation to occur. Increasing extracellular AChE decreased the association of neurexin with neuroligin and inhibited neuroligin-induced synaptogenesis. The number and activity of excitatory synapses in cultured hippocampal neurons were reduced by extracellular catalytically inactive AChE.
  
  
  CONCLUSIONS
  Excessive glycosylated AChE could competitively disrupt a subset of the neurexin-neuroligin junctions consequently impairing the integrity of glutamatergic synapses. This might serve a molecular mechanism of excessive AChE induced neurodegeneration.
authors.forename: Yun-Yan
authors.initials: YY
authors.lastname: Xiang
authors.forename: Haiheng
authors.initials: H
authors.lastname: Dong
authors.forename: Burton B
authors.initials: BB
authors.lastname: Yang
authors.forename: John F
authors.initials: JF
authors.lastname: Macdonald
authors.affiliation: Robarts Research Institute, University of Western Ontario, London, Ontario, Canada. wlu53@uwo.ca.
authors.forename: Wei-Yang
authors.initials: WY
authors.lastname: Lu
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D006031:Glycosylation; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D047468:Immunoprecipitation; D008024:Ligands; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D012326:RNA Splicing; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D005971:Glutamates; D008024:Ligands; D009419:Nerve Tissue Proteins; C086959:neurexin Ibeta; D000110:Acetylcholinesterase