Tags

Type your tag names separated by a space and hit enter

MicroRNA-92 modulates K(+) Cl(-) co-transporter KCC2 expression in cerebellar granule neurons.
J Neurochem. 2010 May; 113(3):591-600.JN

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.

Authors+Show Affiliations

EBRI - European Brain Research Institute - Fondazione EBRI - Rita Levi-Montalcini, Rome, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20050974

Citation

Barbato, Christian, et al. "MicroRNA-92 Modulates K(+) Cl(-) Co-transporter KCC2 Expression in Cerebellar Granule Neurons." Journal of Neurochemistry, vol. 113, no. 3, 2010, pp. 591-600.
Barbato C, Ruberti F, Pieri M, et al. MicroRNA-92 modulates K(+) Cl(-) co-transporter KCC2 expression in cerebellar granule neurons. J Neurochem. 2010;113(3):591-600.
Barbato, C., Ruberti, F., Pieri, M., Vilardo, E., Costanzo, M., Ciotti, M. T., Zona, C., & Cogoni, C. (2010). MicroRNA-92 modulates K(+) Cl(-) co-transporter KCC2 expression in cerebellar granule neurons. Journal of Neurochemistry, 113(3), 591-600. https://doi.org/10.1111/j.1471-4159.2009.06560.x
Barbato C, et al. MicroRNA-92 Modulates K(+) Cl(-) Co-transporter KCC2 Expression in Cerebellar Granule Neurons. J Neurochem. 2010;113(3):591-600. PubMed PMID: 20050974.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-92 modulates K(+) Cl(-) co-transporter KCC2 expression in cerebellar granule neurons. AU - Barbato,Christian, AU - Ruberti,Francesca, AU - Pieri,Massimo, AU - Vilardo,Elisa, AU - Costanzo,Manuela, AU - Ciotti,Maria Teresa, AU - Zona,Cristina, AU - Cogoni,Carlo, Y1 - 2009/12/26/ PY - 2010/1/7/entrez PY - 2010/1/7/pubmed PY - 2010/5/5/medline SP - 591 EP - 600 JF - Journal of neurochemistry JO - J. Neurochem. VL - 113 IS - 3 N2 - 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. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/20050974/MicroRNA_92_modulates_K_+__Cl____co_transporter_KCC2_expression_in_cerebellar_granule_neurons_ L2 - https://doi.org/10.1111/j.1471-4159.2009.06560.x DB - PRIME DP - Unbound Medicine ER -