Cross-talk and co-trafficking between rho1/GABA receptors and ATP-gated channels.
J. Biol. Chem.. 2003-12-01; 279(8): 6967-6975
DOI: 10.1074/jbc.m307772200
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1. J Biol Chem. 2004 Feb 20;279(8):6967-75. Epub 2003 Dec 1.
Cross-talk and co-trafficking between rho1/GABA receptors and ATP-gated channels.
Boué-Grabot E(1), Emerit MB, Toulmé E, Séguéla P, Garret M.
Author information:
(1)CNRS Unité Mixte de Recherche 5543, Université Victor Segalen Bordeaux 2,
33076 Bordeaux cedex, France.
Gamma-aminobutyric-acid (GABA) and ATP ionotropic receptors represent two
structurally and functionally different classes of neurotransmitter-gated
channels involved in fast synaptic transmission. We demonstrate here that, when
the inhibitory rho1/GABA and the excitatory P2X2 receptor channels are
co-expressed in Xenopus oocytes, activation of one channel reduces the currents
mediated by the other one. This reciprocal inhibitory cross-talk is a
receptor-mediated phenomenon independent of agonist cross-modulation, membrane
potential, direction of ionic flux, or channel densities. Functional interaction
is disrupted when the cytoplasmic C-terminal domain of P2X2 is deleted or in
competition experiments with minigenes coding for the C-terminal domain of P2X2
or the main intracellular loop of rho1 subunits. We also show a physical
interaction between P2X2 and rho1 receptors expressed in oocytes and the
co-clustering of these receptors in transfected hippocampal neurons.
Co-expression with P2X2 induces retargeting and recruitment of mainly
intracellular rho1/GABA receptors to surface clusters. Therefore, molecular and
functional cross-talk between inhibitory and excitatory ligand-gated channels may
regulate synaptic strength both by activity-dependent current occlusion and
synaptic receptors co-trafficking.
DOI: 10.1074/jbc.M307772200
PMID: 14660627 [Indexed for MEDLINE]