title: The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum.
abstract: 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.
authors: Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy.
authors: Diego
authors: D
authors: Centonze
authors: Silvia
authors: S
authors: Rossi
authors: Ilaria
authors: I
authors: Napoli
authors: Valentina
authors: V
authors: Mercaldo
authors: Caroline
authors: C
authors: Lacoux
authors: Francesca
authors: F
authors: Ferrari
authors: Maria Teresa
authors: MT
authors: Ciotti
authors: Valentina
authors: V
authors: De Chiara
authors: Chiara
authors: C
authors: Prosperetti
authors: Mauro
authors: M
authors: Maccarrone
authors: Filomena
authors: F
authors: Fezza
authors: Paolo
authors: P
authors: Calabresi
authors: Giorgio
authors: G
authors: Bernardi
authors: Claudia
authors: C
authors: Bagni
mesh_terms: 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
chemical_list: 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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