Selective G protein βγ-subunit compositions mediate phospholipase C activation in the vomeronasal organ

Chemosensory neurons of the vomeronasal organ (VNO) are supposed to detect pheromones controlling social and reproductive behavior in most terrestrial vertebrates. Recent studies indicate that pheromone signaling in VNO neurons is mediated via phospholipase C (PLC) activation generating the two second messengers inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Since Galpha(i) and Galpha(0) predominantly expressed in VNO neurons are usually not involved in activating PLC, it was explored if PLC activation may be mediated by Gbetagamma subunits. It was found that a scavenger for betagamma dinters reduced the urine-induced IP3 formation in VNO preparations in a dose-dependent manner indicating a role for Goy complexes. Towards an identification of the relevant GP and Ggamma subunit(s), PCR approaches as well as immunohistochemical experiments were performed. It was found that out of the five known Go subtypes, only Gbeta(2) was expressed in both Gal as well as Galpha(0). neurons. Experimental approaches focusing on the spatial expression profile of identified Ggamma subtypes revealed that Ggamma(8)-positive neurons are preferentially localized to the basal region of the vomeronasal epithelium, whereas Ggamma(2)-reactive cells are restricted to the apical Galpha(i)-positive layer of the sensory epithelium. As IP3 formation induced upon stimulation with volatile urinary compounds was selectively blocked by Ggamma(2)-specific antibodies whereas second messenger formation elicited upon stimulation with alpha(2u) globulin was inhibited by antibodies recognizing Ggamma(8), it is conceivable that PLC activation in the two populations of chemosensory VNO neurons is mediated by different Gbetagamma complexes.