Role of the scaffolding protein SLC9A3R1 in the vomeronasal organ - from protein interactions to the physiology of pheromone detection

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In most mammals, the vomeronasal system detects of a variety of (semio)chemicals that mediate olfactory-driven social and sexual behaviors. Vomeronasal chemosensation depends on G protein-coupled receptors (V1R, V2R, FPR-rs) that operate at remarkably low stimulus concentrations, thus, indicating a highly sensitive and efficient signaling pathway. We therefore hypothesize a) that vomeronasal signaling cascade proteins are organized in microdomains to ensure optimal signal transduction, and b) that the assembly of these domains involves scaffolding proteins. In the present proposal, we aim to identify and investigate PDZ domain-containing proteins as putative molecular organizers of signal transduction in vomeronasal neurons. Accordingly, a major goal of this research is to analyze the functional role of scaffolding proteins in shaping ultrasensitive and highly selective pheromone responses. SLC9A3R1, a protein that contains two PDZ domains and a carboxy-terminal ezrin-binding domain, is the focus of our interest. We will identify the molecular composition of vomeronasal SLC9A3R1-based scaffolds, study distribution of SLC9A3R1, associated receptor proteins and downstream signaling partners at high resolution, and employ an array of physiological approaches to elucidate the function of protein - protein interactions in vomeronasal signaling.