Figure 8

Schematic of the hypothetical vomeronasal organ transduction model. The vomeronasal organ (VNO) signal transduction pathway begins at either a type 1 vomeronasal (V1R) or type 2 vomeronasal (V2R) G-protein coupled receptor (GPCR); V2Rs may be associated with a member of the M10 major histocompatibility protein family. Upon pheromone binding, the V1R/V2R activates a guanidine trisphosphate-binding protein (G-protein). The activated G-protein stimulates the cleavage of phosphatidylinositol 4,5-bisphosphate (PIP₂) into 1,4,5-inositol trisphosphate (IP₃) and diacylglycerol (DAG) via phospholipase C (PLC). DAG has been reported to gate the non-specific cation current through the type 2 canonical transient receptor potential channel (TRPC2). Although binding of IP₃ to the IP₃ receptor (IP₃R) is not supported to yield a transduction current alone, two isoforms of IP₃R (IP₃R2 and IP₃R3) are expressed in the VNO, and IP₃R3 forms a complex with TRPC2. Whether or not ligand occupancy is required, inhibition of complex formation blocks chemosignal-activated current. TRPC2 expression is increased in the VSN microvillar membrane with the assistance of the chaperone receptor transporting protein 1 (RTP1), whereby the channel associates with both Homer 1b/c and IP₃R3. A calcium activated non-selective ion channel (CaNS) can amplify the chemosignal-induced current following the rise in intracellular calcium. This rise in intracellular calcium also actives calcium-activated big conductance potassium ion channels (BK) as well as calmodulin (CaM), which may bind to both IP₃R3 and TRPC2.