Abstract

Heterotrimeric G-proteins transduce signals from heptahelical transmembrane receptors to different effector systems, regulating diverse complex intracellular pathways and functions. In brain, facilitation of depolarization-induced neurotransmitter release for synaptic transmission is mediated by Gs? and Gq?. To identify effectors for G?-proteins, we performed a yeast two-hybrid screening of a human brain cDNA library, using the human G?s protein as a bait. We identified a protein member of the synembryn family as one of the interacting proteins. Extending the study to other G? subunits, we found that Gq? also interacts with synembryn, and these interactions were confirmed by in vitro pull down studies and by in vivo confocal laser microscopy analysis. Furthermore, synembryn was shown to translocate to the plasma membrane in response to carbachol and isoproterenol. This study supports recent findings in C. elegans where, through genetic studies, synembryn was shown to act together with Gq? regulating neuronal transmitter release. Based on these observations, we propose that synembryn is playing a similar role in human neuronal cells. © 2003 Wiley-Liss, Inc.