The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum.
Dopamine D(2) receptor (D(2)DR)-mediated transmission in the striatum is remarkably flexible, and changes in its efficacy have been heavily implicated in a variety of physiological and pathological conditions. Although receptor-associated proteins are clearly involved in specific forms of synaptic plasticity, the molecular mechanisms regulating the sensitivity of D(2) receptors in this brain area are essentially obscure. We have studied the physiological responses of the D(2)DR stimulations in mice lacking the brain cytoplasmic RNA BC1, a small noncoding dendritically localized RNA that is supposed to play a role in mRNA translation. We show that the efficiency of D(2)-mediated transmission regulating striatal GABA synapses is under the control of BC1 RNA, through a negative influence on D(2) receptor protein level affecting the functional pool of receptors. Ablation of the BC1 gene did not result in widespread dysregulation of synaptic transmission, because the sensitivity of cannabinoid CB(1) receptors was intact in the striatum of BC1 knock-out (KO) mice despite D(2) and CB(1) receptors mediated similar electrophysiological actions. Interestingly, the fragile X mental retardation protein FMRP, one of the multiple BC1 partners, is not involved in the BC1 effects on the D(2)-mediated transmission. Because D(2)DR mRNA is apparently equally translated in the BC1-KO and wild-type mice, whereas the protein level is higher in BC1-KO mice, we suggest that BC1 RNA controls D(2)DR indirectly, probably regulating translation of molecules involved in D(2)DR turnover and/or stability.
Centonze
Diego
D
Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy.
Rossi
Silvia
S
Napoli
Ilaria
I
Mercaldo
Valentina
V
Lacoux
Caroline
C
Ferrari
Francesca
F
Ciotti
Maria Teresa
MT
De Chiara
Valentina
V
Prosperetti
Chiara
C
Maccarrone
Mauro
M
Fezza
Filomena
F
Calabresi
Paolo
P
Bernardi
Giorgio
G
Bagni
Claudia
C
D000818:Animals; D000831:Animals, Newborn; D001713:Biphenyl Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology*; D065127:Dopamine D2 Receptor Antagonists; D005968:Glutamate Decarboxylase / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009841:Oligonucleotides / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010879:Piperazines / Q000494:pharmacology; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000096:biosynthesis; D022661:RNA, Untranslated; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000737:chemistry / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D020736:Ribonucleoproteins, Small Cytoplasmic / Q000172:deficiency / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C076675:Bc1 long-non-coding RNA, mouse; D001713:Biphenyl Compounds; D065127:Dopamine D2 Receptor Antagonists; D007527:Isoenzymes; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D009841:Oligonucleotides; D010879:Piperazines; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; D017448:Receptors, Dopamine D2; D020736:Ribonucleoproteins, Small Cytoplasmic; C105771:GR 103691; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2
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