Nature Reviews Neuroscience - Highlights
June 2001 Vol 2 No 6 HIGHLIGHTS
Nature Reviews Neuroscience 2, 380 (2001); doi:10.1038/35077522
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GLIA
Crystal-clear glia­neuron interactions
Juan Carlos López
The profound effect that glial cells have on neurotransmission continues to
gain notoriety; hardly a month passes without an important breakthrough in
this flourishing field. The latest development has come from the study of
acetylcholine (ACh)-mediated transmission in the snail Lymnaea stagnalis. In
this system, Smit et al. have identified an ACh-binding protein (AChBP)
released by glia, which can directly modulate the efficacy of synaptic
transmission.
The authors observed
that if a presynaptic
neuron was stimulated
repeatedly, the presence
of a glial cell around the
synapse caused a
reduction in the
postsynaptic, ACh-
dependent response. By
analysing this modulation
in detail, Smit et al.
determined that the glial
cell responded to ACh
and released AChBP,
which then acted as a
molecular decoy, binding
the transmitter and
reducing its availability at
the synapse.
AChBP shows significant
sequence homology to
members of the ligand-
gated ion-channel (LGIC) family. In particular, AChBP resembles the ligand-
binding site of nicotinic ACh receptors. In a companion paper, Brejc et al.
report that they have solved the crystal structure of AChBP and, indirectly,
gained new insights into the atomic structure of the ACh-receptor binding
site. As predicted for the ACh receptor, AChBP forms pentamers in which the
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Nature Reviews Neuroscience - Highlights
ligand-binding site is located at the interface between subunits. The authors
identified the residues that form the binding site and noted that they are
quite variable among LGICs, reflecting perhaps their different binding
properties. By contrast, residues conserved between AChBP and LGICs do
not contribute to ligand binding but seem to stabilize the global structure of
each subunit.
So, in addition to re-emphasizing the influence of glial cells on
neurotransmission, the study of AChBP constitutes a double triumph,
providing the first detailed three-dimensional account of the ACh binding
site. This information will have a great influence on the structural analysis of
other LGICs, comparable only to the impact that the structure of KcsA has
had on the study of other voltage-gated ion channels.
References and links
ORIGINAL RESEARCH PAPER
Smit, A. B. et al. A glia-derived acetylcholine-binding protein that modulates
synaptic transmission. Nature 411, 261-268 (2001). | Article
| PubMed | ISI | ChemPort |
Brejc, K. Crystal structure of an ACh-binding protein reveals the ligand-
binding domain of nicotinic receptors. Nature 411, 269-276 (2001). | Article
| PubMed | ISI | ChemPort |
FURTHER READING
Haydon, P. G. Glia: listening and talking to the synapse. Nature Rev.
Neurosci. 2, 185-193 (2001) | Article | PubMed | ISI | ChemPort |
Corringer, P. J. et al. Nicotinic receptors at the amino-acid level. Annu. Rev.
Pharmacol. Toxicol. 40, 431-458 (2000) | Article | PubMed | ISI | ChemPort |
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