Gap junctional control of glial glutamate transporter expression.

TY - JOUR

T1 - Gap junctional control of glial glutamate transporter expression.

AU - Figiel, Maciej

AU - Allritz, Claudia

AU - Lehmann, Claudia

AU - Engele, Jürgen

PY - 2007

Y1 - 2007

N2 - The uptake of glutamate into astroglia is the predominant mechanism to terminate glutamatergic neurotransmission and to prevent neurotoxic extracellular glutamate concentrations. Here, we show that uncoupling cultured cortical astrocytes with the gap junction blocker, propofol, or the Cx43 mimetic peptide, Gap27, inhibits the expression of GLT-1, the major glutamate transporter subtype in the cortex. The dependence of GLT-1 expression on gap junctions was further confirmed by the use of astrocytes in which either the expression of Cx43, the major astrocytic gap junction protein, was inhibited by RNA interference or which were derived from animals carrying an astrocyte-specific deletion of the Cx43 gene. In both cases, reduced astrocytic coupling was associated with a pronounced decline in GLT-1 expression. Finally, a luciferase reporter gene assay demonstrated that blockade of gap junctions/connexins suppressed transcriptional activity of GLT-1 promoter. These observations unravel a previously unrecognized role of gap junctions in the control of glial glutamate transport.

AB - The uptake of glutamate into astroglia is the predominant mechanism to terminate glutamatergic neurotransmission and to prevent neurotoxic extracellular glutamate concentrations. Here, we show that uncoupling cultured cortical astrocytes with the gap junction blocker, propofol, or the Cx43 mimetic peptide, Gap27, inhibits the expression of GLT-1, the major glutamate transporter subtype in the cortex. The dependence of GLT-1 expression on gap junctions was further confirmed by the use of astrocytes in which either the expression of Cx43, the major astrocytic gap junction protein, was inhibited by RNA interference or which were derived from animals carrying an astrocyte-specific deletion of the Cx43 gene. In both cases, reduced astrocytic coupling was associated with a pronounced decline in GLT-1 expression. Finally, a luciferase reporter gene assay demonstrated that blockade of gap junctions/connexins suppressed transcriptional activity of GLT-1 promoter. These observations unravel a previously unrecognized role of gap junctions in the control of glial glutamate transport.

M3 - SCORING: Zeitschriftenaufsatz

VL - 35

SP - 130

EP - 137

JO - MOL CELL NEUROSCI

JF - MOL CELL NEUROSCI

SN - 1044-7431

IS - 1

M1 - 1

ER -