GABAB receptor subunit GB1 at the cell surface independently activates ERK1/2 through IGF-1R transactivation

Abstract

Background: Functional GABAB receptor is believed to require hetero-dimerization between GABAB1 (GB1) and GABAB2 (GB2) subunits. The GB1 extracellular domain is required for ligand binding, and the GB2 trans-membrane domain is responsible for coupling to G proteins. Atypical GABAB receptor responses observed in GB2-deficient mice suggested that GB1 may have activity in the absence of GB2. However the underlying mechanisms remain poorly characterized. Methodology/Principal Findings: Here, by using cells overexpressing a GB1 mutant (GB1asa) with the ability to translocate to the cell surface in the absence of GB2, we show that GABAB receptor agonists, such as GABA and Baclofen, can induce ERK1/2 phosphorylation in the absence of GB2. Furthermore, we demonstrate that GB1asa induces ERK1/2 phosphorylation through Gi/o proteins and PLC dependent IGF-1R transactivation. Conclusions/Significance: Our data suggest that GB1 may form a functional receptor at the cell surface in the absence of GB2. © 2012 Baloucoune et al.