TY - JOUR

T1 - GABAB receptors couple directly to the transcription factor ATF4

AU - Vernon, Ellen

AU - Meyer, G

AU - Pickard, L

AU - Dev, K

AU - Molnar, E

AU - Collingridge, G

AU - Henley, JM

PY - 2001/4

Y1 - 2001/4

N2 - The inhibitory neurotransmitter gamma-aminobutyric acid (GABA), acts at ionotropic (GABA(A) and GABA(C)) and metabotropic (GABA(B)) receptors. Functional GABA(B) receptors are heterodimers of GABA(B(1)) and GABA(B(2)) subunits. Here we show a robust, direct, and specific interaction between the coiled-coil domain present in the C-terminus of the GABA(B(1)) subunit and the transcription factor ATF4 (also known as CREB2). ATF4 and GABA(B(2)) binding to the GABA(B(1)) subunit were mutually exclusive. In rat hippocampal neurons native GABA(B(1)) showed surprisingly little similarity to GABA(B(2)) in its subcellular distribution. GABA(B(1)) and ATF4, however, were highly colocalized throughout the cell and displayed a punctate distribution within the dendrites. Activation of GABA(B) receptors in hippocampal neurons caused a dramatic translocation of ATF4 out of the nucleus into the cytoplasm. These data suggest a novel neuronal signaling pathway that could regulate the functional expression of GABA(B) receptors and/or modulate gene transcription.

AB - The inhibitory neurotransmitter gamma-aminobutyric acid (GABA), acts at ionotropic (GABA(A) and GABA(C)) and metabotropic (GABA(B)) receptors. Functional GABA(B) receptors are heterodimers of GABA(B(1)) and GABA(B(2)) subunits. Here we show a robust, direct, and specific interaction between the coiled-coil domain present in the C-terminus of the GABA(B(1)) subunit and the transcription factor ATF4 (also known as CREB2). ATF4 and GABA(B(2)) binding to the GABA(B(1)) subunit were mutually exclusive. In rat hippocampal neurons native GABA(B(1)) showed surprisingly little similarity to GABA(B(2)) in its subcellular distribution. GABA(B(1)) and ATF4, however, were highly colocalized throughout the cell and displayed a punctate distribution within the dendrites. Activation of GABA(B) receptors in hippocampal neurons caused a dramatic translocation of ATF4 out of the nucleus into the cytoplasm. These data suggest a novel neuronal signaling pathway that could regulate the functional expression of GABA(B) receptors and/or modulate gene transcription.

U2 - 10.1006/mcne.2000.0960

DO - 10.1006/mcne.2000.0960

M3 - Article

VL - 17

SP - 637

EP - 645

JO - Molecular and Cellular Neuroscience

JF - Molecular and Cellular Neuroscience

SN - 1044-7431

IS - 4

ER -