MicroRNA-92 modulates K(+) Cl(-) co-transporter KCC2 expression in cerebellar granule neurons (Articolo in rivista)

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  • MicroRNA-92 modulates K(+) Cl(-) co-transporter KCC2 expression in cerebellar granule neurons (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1111/j.1471-4159.2009.06560.x (literal)
Alternative label
  • Barbato C. 1, 2, Ruberti F. 1, Pieri M. 3,4, Vilardo E. 1, Costanzo M. 1, Ciotti M.T. 1, Zona C. 3,4, Cogoni C. 1,5 (2010)
    MicroRNA-92 modulates K(+) Cl(-) co-transporter KCC2 expression in cerebellar granule neurons
    in Journal of neurochemistry; John Wiley & Sons Inc., Hoboken (Stati Uniti d'America)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Barbato C. 1, 2, Ruberti F. 1, Pieri M. 3,4, Vilardo E. 1, Costanzo M. 1, Ciotti M.T. 1, Zona C. 3,4, Cogoni C. 1,5 (literal)
Pagina inizio
  • 591 (literal)
Pagina fine
  • 600 (literal)
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  • 2009 Dec 26. [Epub ahead of print] (literal)
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  • http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2009.06560.x/abstract (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 113/3 (literal)
Rivista
Note
  • Scopu (literal)
  • PubMe (literal)
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  • 1 - EBRI – European Brain Research Institute – Fondazione EBRI – Rita Levi-Montalcini, Rome, Italy; 2 - INMM – Istituto di Neurobiologia e Medicina Molecolare, CNR, Rome, Italy; 3 - Department of Neuroscience, University of Rome 'Tor Vergata', Rome, Italy; 4 - Fondazione S. Lucia, I.R.C.C.S., Rome, Italy; 5 - Dipartimento di Biotecnologie Cellulari ed Ematologia, Università di Roma 'La Sapienza', Rome, Italy Address correspondence and reprint requests to Francesca Ruberti, INMM – Istituto di Neurobiologia e (literal)
Titolo
  • MicroRNA-92 modulates K(+) Cl(-) co-transporter KCC2 expression in cerebellar granule neurons (literal)
Abstract
  • Abstract MicroRNAs have been associated to fine-tuning spatial and temporal control of gene expression during neuronal development. The neuronal Cl(-) extruding, K(+)Cl(-) co-transporter 2 (KCC2) is known to play an important role in neuronal Cl(-) homeostasis and in determining the physiological response to activation of anion selective GABA receptors. Here we show that microRNA-92 is developmentally down-regulated during maturation of rat cerebellar granule neurons (CGNs) in vitro. Computational predictions suggest several high-ranking targets for microRNA-92 including the KCC2 gene. Consistently, the KCC2 protein levels were up-regulated in mature CGN in vitro and a functional association between microRNA-92 and KCC2 3' untranslated region was established using luciferase assays. The generation of an inward directed Cl(-) electrochemical gradient, necessary for the hyperpolarizing effect of GABA, requires robust KCC2 expression in several neuronal types. Here we show that lentiviral-mediated microRNA-92 over-expression reduced KCC2 protein levels and positively shifted reversal potential of GABA induced Cl(-) currents in CGNs. In addition KCC2 re-expression reversed microRNA-92 electrophysiological phenotype. Consistently microRNA-92 inhibition induced both an increase of the level of KCC2 and a negative shift in GABA reversal potential. These findings introduce a new player in the developmental change of GABA from depolarization to hyperpolarization. (literal)
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