Sensory Transduction in the Vomeronasal Organ

This dissertation discusses signal transduction cascades in the vomeronasal organ (VNO) of the stinkpot turtle, Sternotherus odoratus and the Sprague-Dawley rat by investigating downstream signaling events leading to a vomeronasal receptor potential in response to a species-specific chemical. The VNO is the receptor portion of a distinct olfactory system found in most vertebrates that normally functions to detect socially relevant chemical cues. It is thought that chemical communication is transduced when a ligand (chemical or pheromone) binds to a G protein-coupled receptor (GPCR) in the plasma membrane of a vomeronasal sensory neuron (VSN). The G protein-coupled receptors are located on microvillar processes of the dendrites of VSNs, the same place where G protein Gai2 and the transient receptor potential channel (TRPC2) have been localized. The transduction event (or events) in between binding of the chemical odorant to the final electrical event via any of these transduction elements has not been shown. Phosphoinositide signaling is intricately connected to the proper sequestration of calcium and its release from intracellular stores. Here, I discuss both voltage- and chemically-activated properties of VSNs isolated from the VNO of S. odoratus, including measurements of conductance changes with odor application and reversal potential analysis. I provide evidence for the expression of three GTP binding proteins in the VNO of the Chilean lizard of the genus Liolaeumus. I also demonstrate TRPC2 and type III inositol 1,4,5-trisphosphate receptor (IP3R3) participate in a protein-protein interaction in the rodent VNO. Interrupting the interaction between TRPC2 and IP3R3 results in a decreased odor response over ten minutes. Blocking the enzyme phospholipase C (PLC) also results in a loss of the odor response. A third member of the signaling complex, Homer, was shown to participate in a protein-protein interaction with TRPC2 and IP3R3. These proteins, TRPC2, IP3R3 and Homer, form part of a signalplex that likely brings the GPCR and the signaling apparatus in close proximity in the VSN so chemical detection occurs with rapidity and reliability. The signalplex also likely functions to properly localize TRPC2 in both species, and may modulate its function with seasonality, in the case of S. odoratus.