P2X receptor trafficking in neurons is subunit specific.
P2X receptors within the CNS mediate excitatory synaptic transmission and also act presynaptically to modulate neurotransmitter release. We have studied the targeting and trafficking of P2X4 and P2X2 receptors heterologously expressed in cultured olfactory bulb neurons. Homomeric P2X4 receptors had a punctate distribution, and many of the puncta colocalized with early endosomes. In contrast, P2X2 receptors were primarily localized at the plasma membrane. By antibody-labeling of surface receptors in living neurons, we showed that P2X4 receptors undergo rapid constitutive internalization and subsequent reinsertion into the plasma membrane, whereas P2X2 receptors were not regulated in such a way. The internalization of P2X4 receptors was dynamin-dependent, and the binding of ATP enhanced the basal rate of retrieval in a Ca2+-independent manner. The presence of the P2X4 subunit in a P2X4/6 heteromer governed the trafficking properties of the receptor. P2X receptors acted presynaptically to enhance the release of glutamate, suggesting that the regulated cycling of P2X4-containing receptors might provide a mechanism for modulation of synaptic transmission.
Bobanovic
Laura K
LK
Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, United Kingdom.
Royle
Stephen J
SJ
Murrell-Lagnado
Ruth D
RD
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D034281:Dynamins; D004705:Endocytosis; D020558:GTP Phosphohydrolases / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism*; D021122:Protein Subunits; D021381:Protein Transport; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000032:analysis / Q000378:metabolism*; D058476:Receptors, Purinergic P2X2; D058848:Receptors, Purinergic P2X4; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission
C546401:P2RX2 protein, human; C548226:P2RX4 protein, human; D021122:Protein Subunits; D058910:Purinergic P2 Receptor Agonists; D017661:Receptors, Presynaptic; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D058848:Receptors, Purinergic P2X4; C110590:purinoceptor P2X6; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D020558:GTP Phosphohydrolases; D034281:Dynamins