Association of GABAB Receptors and Members of the 14-3-3 Family of Signaling Proteins - ScienceDirect

Molecular and Cellular Neuroscience

Volume 17, Issue 2, February 2001, Pages 317-328

Molecular and Cellular Neuroscience

https://doi.org/10.1006/mcne.2000.0938 Get rights and content

Abstract

Two GABA_B receptors, GABA_BR1 and GABA_BR2, have been cloned recently. Unlike other G protein-coupled receptors, the formation of a heterodimer between GABA_BR1 and GABA_BR2 is required for functional expression. We have used the yeast two hybrid system to identify proteins that interact with the C-terminus of GABA_BR1. We report a direct association between GABA_B receptors and two members of the 14-3-3 protein family, 14-3-3η and 14-3-3ζ. We demonstrate that the C-terminus of GABA_BR1 associates with 14-3-3ζ in rat brain preparations and tissue cultured cells, that they codistribute after rat brain fractionation, colocalize in neurons, and that the binding site overlaps partially with the coiled-coil domain of GABA_BR1. Furthermore we show a reduced interaction between the C-terminal domains of GABA_BR1 and GABA_BR2 in the presence of 14-3-3. The results strongly suggest that GABA_BR1 and 14-3-3 associate in the nervous system and begin to reveal the signaling complexities of the GABA_BR1/GABA_BR2 receptor heterodimer.

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