Identifying Key Regulators in Odorant Receptor Trafficking

Odor detection in mammals is primarily mediated by odorant receptors (ORs), the largest family of G-protein-coupled receptors, expressed in olfactory sensory neurons (OSNs; Buck and Axel, 1991). However, most ORs exhibit little or no cell surface expression in nonolfactory cell types (Lu et al., 2003; Hague et al., 2004). While the accessory protein RTP1 and RTP2 enhance the expression of certain ORs, we hypothesized that additional proteins coregulated with RTP1 and RTP2 during OSN maturation may further enhance OR cell surface expression (Saito et al., 2004; Zhuang and Matsunami, 2007). To test this, we developed a computational pipeline based on publicly available single-cell transcriptomic data to create an interactive tool for exploring gene expression during OSN maturation. Using this tool, we identified genes coregulated with Rtp1 during olfactory development. Three genes-Gfy, Clgn, and Syt1-exhibited transcriptional profiles similar to Rtp1. When coexpressed with an OR, these genes, in combination with Rtp1, promoted cell-surface expression of the tested ORs. Importantly, we demonstrated a physical interaction between Syt1 and an OR (Or1ad1) via co-immunoprecipitation, suggesting a novel role for Syt1 in OR trafficking or stabilization. We also observed localization of Syt1 protein in OSN cilia in both male and female mice. Together, these findings provide new insights into OSN development and the molecular mechanisms underlying OR biogenesis, paving the way for further research into the functional regulation of the olfactory systems.