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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / metabolism*
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Acetylcholine / pharmacology
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Amino Acid Sequence
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Animals
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Bungarotoxins / metabolism
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Bungarotoxins / pharmacology
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Carrier Proteins / pharmacology
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Cells, Cultured
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Central Nervous System / cytology
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Central Nervous System / metabolism
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Coculture Techniques
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Inhibitory Concentration 50
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Ligands
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Lymnaea* / chemistry
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Lymnaea* / genetics
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Lymnaea* / physiology
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Models, Neurological
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Molecular Sequence Data
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Neuroglia / chemistry
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Neuroglia / cytology
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Neuroglia / drug effects
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Neuroglia / metabolism*
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Protein Binding
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Protein Sorting Signals
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Protein Structure, Quaternary
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Protein Structure, Tertiary
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Protein Transport
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RNA, Messenger / analysis
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RNA, Messenger / genetics
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Receptors, Nicotinic / chemistry
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Receptors, Nicotinic / metabolism
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Sequence Alignment
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Serotonin / metabolism
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Serotonin / pharmacology
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Synaptic Transmission* / drug effects
Substances
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AChBP protein, Lymnaea
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Bungarotoxins
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Carrier Proteins
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Ligands
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Protein Sorting Signals
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RNA, Messenger
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Receptors, Nicotinic
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Serotonin
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Acetylcholine