Role of olfactory receptor Olfr544 in neuronal cells: Insights into neurite outgrowth and CREB signaling.

Olfactory receptors (ORs) are expressed beyond the nasal epithelium and implicated in brain function, yet their roles remain unclear. This study investigated the function of the OR Olfr544, which has been reported to be highly expressed near amyloid plaques in Alzheimer's disease model mice, using the mouse neuroblastoma N2a cell line. We found that its agonist azelaic acid (AZA) promotes neurite outgrowth and activates the cAMP-PKA-CREB signaling cascade in an Olfr544-dependent manner. Transcriptome analysis of Olfr544-knockout cells revealed altered expression of genes involved in neuroactive signaling and cytoskeletal organization. Key downstream targets, including Igf2bp3, were identified and validated. These results establish a functional link between an extra-olfactory OR and neuronal morphology via CREB in vitro, providing a mechanistic basis for further studies of OR functions in the nervous system.