Activation of SRE and AP1 by olfactory receptors via the MAPK and Rho dependent pathways.

Whereas the activation of MAPKs (mitogen activated kinases) and Rho dependant pathways by GPCR (G protein coupled receptors) has been the subject of many studies, its implication in the signalling of olfactory receptors, which constitute the largest GPCR family, has been far less analysed. Using an in vitro heterologous system, we showed that odorant activated ORs activate SRE containing promoters via the ERK pathway. We also demonstrated that RhoA and Rock kinases but not Rac were involved in ORs-induced SRE/SRF activation and that AP1 was activated, via JNK and p38 MAPKinase. Using real time PCR we found that mOR23, RnI7 and CfOR12A07 induced elevated levels of transcription factors ELK-4, srf, c-fos and c-jun mRNAs whereas mOREG induced an elevated transcription levels of c-fos and c-jun mRNA only. We showed also that odorant activated ORs stimulate the downstream MAPKs and Rho pathways in primary cultures of rat olfactory sensory neurons (OSNs). Similar results were also obtained with OE (olfactory epithelium) extracts prepared from rats exposed to odorants in vivo. Finally, we showed the important role of the AKT and MAPK signalling pathways in OSNs survival. Taken together, these data provide direct evidence that the binding of odorants onto their ORs activates the MAPK and Rho signalling pathways that are involved in OSNs survival events. This suggests that these pathways could be implicated in the regulation of OSNs homeostasis.