Gene expression profiling of vomeronasal organ in Cnpy1 knockout and wildtype mice.

Distinct families of V1R or V2R type GPCRs G-protein coupled receptors (GPCRs) are expressed in the mouse vomeronasal organ within spatially segregated vomeronasal sensory neurons (VSNs) that are also identified by the expression of cognate G-protein subunits, Gαi2 or Gαo. How vomeronasal GPCRs detect chemo-signals important for innate social and reproductive behaviors, requires understanding the molecular and cellular diversification accompanying VSN differentiation from a stem cell population. Here, we identify mouse Cnpy1 as a novel VNO specific ER chaperone, with expression restricted to Gαo VSNs. Absence of Cnpy1 leads to reduced neuronal activation, behavioral defects and a substantial loss of neurons by apoptosis during postnatal development. Co-immunoprecipitation followed by mass spectrometry, identified specific interactions of Cnpy1 with V2R GPCRs along with other ER chaperones. Together with our earlier findings of hypertrophic and gyroid ER in Gαo neurons, these results highlight a critical role for ER chaperones and ER architecture, necessary for the proper function of Gαo sensory neurons.