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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.

SUBMITTER: Centonze D 

PROVIDER: S-EPMC6672174 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature

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The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum.

Centonze Diego D   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  

The Journal of neuroscience : the official journal of the Society for Neuroscience 20070801 33


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 m  ...[more]

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