GABA(B) receptors couple directly to the transcription factor ATF4.
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.
Vernon
E
E
MRC Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, Bristol University, University Walk, Bristol, BS8 1TD.
Meyer
G
G
Pickard
L
L
Dev
K
K
Molnar
E
E
Collingridge
G L
GL
Henley
J M
JM
D051701:Activating Transcription Factor 4; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002451:Cell Compartmentation / Q000502:physiology; D002460:Cell Line; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007668:Kidney / Q000166:cytology; D016350:Leucine Zippers / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D017434:Protein Structure, Tertiary; D018080:Receptors, GABA-B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D014162:Transfection
C497109:ATF4 protein, human; D018080:Receptors, GABA-B; D014157:Transcription Factors; D051701:Activating Transcription Factor 4