title: A glia-derived acetylcholine-binding protein that modulates synaptic transmission.
abstract: There is accumulating evidence that glial cells actively modulate neuronal synaptic transmission. We identified a glia-derived soluble acetylcholine-binding protein (AChBP), which is a naturally occurring analogue of the ligand-binding domains of the nicotinic acetylcholine receptors (nAChRs). Like the nAChRs, it assembles into a homopentamer with ligand-binding characteristics that are typical for a nicotinic receptor; unlike the nAChRs, however, it lacks the domains to form a transmembrane ion channel. Presynaptic release of acetylcholine induces the secretion of AChBP through the glial secretory pathway. We describe a molecular and cellular mechanism by which glial cells release AChBP in the synaptic cleft, and propose a model for how they actively regulate cholinergic transmission between neurons in the central nervous system.
authors.affiliation: Department of Molecular and Cellular Neurobiology, Research Institute Neurosciences Vrije Universiteit, Faculty of Biology, De Boelelaan 1087, 1081 HV Amsterdam, The Netherlands. absmit@bio.vu.nl
authors.forename: A B
authors.initials: AB
authors.lastname: Smit
authors.forename: N I
authors.initials: NI
authors.lastname: Syed
authors.forename: D
authors.initials: D
authors.lastname: Schaap
authors.forename: J
authors.initials: J
authors.lastname: van Minnen
authors.forename: J
authors.initials: J
authors.lastname: Klumperman
authors.forename: K S
authors.initials: KS
authors.lastname: Kits
authors.forename: H
authors.initials: H
authors.lastname: Lodder
authors.forename: R C
authors.initials: RC
authors.lastname: van der Schors
authors.forename: R
authors.initials: R
authors.lastname: van Elk
authors.forename: B
authors.initials: B
authors.lastname: Sorgedrager
authors.forename: K
authors.initials: K
authors.lastname: Brejc
authors.forename: T K
authors.initials: TK
authors.lastname: Sixma
authors.forename: W P
authors.initials: WP
authors.lastname: Geraerts
mesh_terms: D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism / Q000494:pharmacology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism; D018920:Coculture Techniques; D020128:Inhibitory Concentration 50; D008024:Ligands; D008195:Lymnaea / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D008959:Models, Neurological; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D021382:Protein Sorting Signals; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: C428944:AChBP protein, Lymnaea; D002038:Bungarotoxins; D002352:Carrier Proteins; D008024:Ligands; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D012701:Serotonin; D000109:Acetylcholine