A glia-derived acetylcholine-binding protein that modulates synaptic transmission

Nature. 2001 May 17;411(6835):261-8. doi: 10.1038/35077000.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Acetylcholine / pharmacology
  • Amino Acid Sequence
  • Animals
  • Bungarotoxins / metabolism
  • Bungarotoxins / pharmacology
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Carrier Proteins / pharmacology
  • Cells, Cultured
  • Central Nervous System / cytology
  • Central Nervous System / metabolism
  • Coculture Techniques
  • Inhibitory Concentration 50
  • Ligands
  • Lymnaea* / chemistry
  • Lymnaea* / genetics
  • Lymnaea* / physiology
  • Models, Neurological
  • Molecular Sequence Data
  • Neuroglia / chemistry
  • Neuroglia / cytology
  • Neuroglia / drug effects
  • Neuroglia / metabolism*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Protein Binding
  • Protein Sorting Signals
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Protein Transport
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Receptors, Nicotinic / chemistry
  • Receptors, Nicotinic / metabolism
  • Sequence Alignment
  • Serotonin / metabolism
  • Serotonin / pharmacology
  • Synaptic Transmission* / drug effects

Substances

  • AChBP protein, Lymnaea
  • Bungarotoxins
  • Carrier Proteins
  • Ligands
  • Protein Sorting Signals
  • RNA, Messenger
  • Receptors, Nicotinic
  • Serotonin
  • Acetylcholine