OR51E2, an olfactory receptor, belongs to the class A G protein-coupled receptors (GPCRs). It plays a key role in the sense of smell by recognizing odorants like fatty acids. In non-olfactory tissues, it is involved in various physiological processes and diseases. For example, it is ectopically expressed in prostate tissues and is associated with prostate cancer progression, and is also expressed in parafollicular C-cells of the thyroid, being a potential diagnostic and therapeutic target for medullary thyroid cancer [1,2,3].

In the study of Olfr-78 (mouse counterpart of OR51E2), Olfr-78 knockout mice showed increased expression of IL-1β and inflammatory signs in the colon compared to control mice when administered with dextran sodium sulfate (DSS), suggesting that OR51E2 may play a role in modulating the intestinal response to colitis [4]. In prostate cancer cells, CRISPR-Cas9-mediated knockout of components in the Gβγ-PI3Kγ-ARF1 pathway abolished ERK1/2 activation by β-ionone, an OR51E2 agonist, indicating OR51E2 activates ERK1/2 through this Golgi-localized pathway [2].

In conclusion, OR51E2 is crucial in both olfactory and non-olfactory biological processes. The use of gene knockout models, such as the Olfr-78 knockout mouse model, has provided insights into its role in diseases like colitis and the signaling pathways related to cancer, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Wu, Chenyang, Xu, Marc, Dong, Junlin, Cui, Wenqiang, Yuan, Shuguang. 2024. The structure and function of olfactory receptors. In Trends in pharmacological sciences, 45, 268-280. doi:10.1016/j.tips.2024.01.004. https://pubmed.ncbi.nlm.nih.gov/38296675/

2. Xu, Xin, Khater, Mostafa, Wu, Guangyu. 2022. The olfactory receptor OR51E2 activates ERK1/2 through the Golgi-localized Gβγ-PI3Kγ-ARF1 pathway in prostate cancer cells. In Frontiers in pharmacology, 13, 1009380. doi:10.3389/fphar.2022.1009380. https://pubmed.ncbi.nlm.nih.gov/36313302/

3. Lee, Hyeon Jeong, Ku, Cheol Ryong, Cho, Arthur, Koo, JaeHyung, Lee, Eun Jig. 2023. Acetate-Mediated Odorant Receptor OR51E2 Activation Results in Calcitonin Secretion in Parafollicular C-Cells: A Novel Diagnostic Target of Human Medullary Thyroid Cancer. In Biomedicines, 11, . doi:10.3390/biomedicines11061688. https://pubmed.ncbi.nlm.nih.gov/37371783/

4. Kotlo, Kumar, Anbazhagan, Arivarasu N, Priyamvada, Shubha, Dudeja, Pradeep K, Layden, Brian T. 2020. The olfactory G protein-coupled receptor (Olfr-78/OR51E2) modulates the intestinal response to colitis. In American journal of physiology. Cell physiology, 318, C502-C513. doi:10.1152/ajpcell.00454.2019. https://pubmed.ncbi.nlm.nih.gov/31913697/