Cross-talk and co-trafficking between rho1/GABA receptors and ATP-gated channels.
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.
Boué-Grabot
Eric
E
CNRS Unité Mixte de Recherche 5543, Université Victor Segalen Bordeaux 2, 33076 Bordeaux cedex, France. eric.boue-grabot@umr5543.u-bordeaux2.fr
Emerit
Michel B
MB
Toulmé
Estelle
E
Séguéla
Philippe
P
Garret
Maurice
M
D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004594:Electrophysiology; D007150:Immunohistochemistry; D007477:Ions; D008024:Ligands; D008564:Membrane Potentials; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D018080:Receptors, GABA-B / Q000737:chemistry* / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000737:chemistry; D058476:Receptors, Purinergic P2X2; D014162:Transfection; D014981:Xenopus / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology; D020741:rho GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism
D007477:Ions; D008024:Ligands; D018080:Receptors, GABA-B; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate; D020741:rho GTP-Binding Proteins; D002118:Calcium