Chemokine receptor CXCR2 regulates the functional properties of AMPA-type glutamate receptor GluR1 in HEK cells.
Experiments were conducted in both HEK cells and cerebellar neurons to investigate whether CXC chemokine receptor 2 (CXCR2) is functionally coupled to GluR1. The co-expression of CXCR2 with GluR1 in HEK cells increased (i) the GluR1 "apparent" affinity for the transmitter; (ii) the GluR1 channel open probability; and (iii) GluR1 binding site cooperativity upon CXCR2 stimulation with CXC chemokine ligand 2 (CXCL2). The affinity of C-terminal-deleted GluR1 for glutamate (Glu) remained stable instead. Furthermore, CXCL2 increased the binding site cooperativity of AMPA receptors in rat cerebellar granule cells; and the amplitude of spontaneous excitatory postsynaptic current (sEPSCs) in Purkinje neurons (PNs). Our findings indicate that the coupling of CXCR2 with GluR1 may modulate glutamatergic synaptic transmission.
Lax
P
P
Dipartimento di Fisiologia Umana e Farmacologia, Università di Roma, Piazzale Aldo Moro 5, I00185, Rome, Italy.
Limatola
C
C
Fucile
S
S
Trettel
F
F
Di Bartolomeo
S
S
Renzi
M
M
Ragozzino
D
D
Eusebi
F
F
D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism*; D002525:Cerebellar Cortex / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000276:immunology; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013569:Synapses / Q000276:immunology / Q000378:metabolism*; D009435:Synaptic Transmission / Q000276:immunology*
D019743:Chemokines, CXC; D018076:DNA, Complementary; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D007473:Ion Channels; D018091:Receptors, AMPA; D023063:Receptors, Interleukin-8B