Effectors of Gα_o

Neuronal differentiation is a complex process that integrates many signals to drive electrophysiological, morphological, and transcriptional changes. The molecular signals of many hormones, neurotransmitters, and chemokines are converted into intracellular responses by G-protein-coupled receptors. This chapter focuses on signals from Gi/o-coupled receptors that regulate neurite outgrowth during neuronal differentiation, and their potential implications in neuronal survival after injury. The function of the α subunit of Go has remained elusive despite the fact that it is the most abundant G protein in the brain. Recent studies have begun to elucidate the mechanistic details of Gαo signaling, and it has proven difficult to identify direct effectors of Gαo. Several studies demonstrate that Gαo signaling activates Src-STAT3 pathway that triggers cell transformation in NIH-3T3 fibroblasts. This chapter also discusses the roles of Rap1GAPII and GRIN in Go signaling during neurite outgrowth. The ligands that stimulate Gi/o-coupled receptors and the effectors that are activated are summarized. Several in vitro and in vivo studies have reported that cannabinoids can protect neural cells from different insults, such as glutamatergic excitotoxicity, oxidative damage, traumatic injury, and ischemia. Some of the more recent studies shed light on the importance of the PI3K/Akt pathway as a connective link between Gαo signaling and neuroprotection.