A Testis ER Chaperone Marks Mature Olfactory and Vomeronasal Sensory Neurons

The proper folding of most secreted and membrane proteins involves interaction with endoplasmic reticulum-resident, glycan-binding chaperones. Some of these chaperones, such as Calreticulin and Calnexin, are nearly ubiquitous, while others are found only in specific cell types, presumably reflecting a role in biosynthesis of proteins specific to those cells. Herein, I have identified Calmegin (Clgn), a chaperone required for fertile spermatogenesis, as a marker of mature neurons in the olfactory system. CLGN was expressed by olfactory marker protein (OMP)-positive neurons in both the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). CLGN was detected both in the perinuclear ER network and in axons. Finally expression of Atf5, a transcription factor required for OSN and VSN development, was both required and sufficient for robust CLGN expression in OSNs and VSNs. Together these findings establish that an ER chaperone required for sperm fertility is developmentally regulated in olfactory neurons, provide a novel marker of mature olfactory neurons, and suggest common mechanisms of secretory protein biogenesis in these cell types.