Eph receptors, which bind to the ephrin ligand, are the largest receptor tyrosine kinase (RTK) family. The structure of the Eph receptor, which is typical of those in the RTK family, consists of an extracellular region where ephrin will bind, a transmembrane segment, and an intracellular region in the cytoplasm containing the kinase domain (EPH Receptor Signaling and Ephrins). The Eph family is further categorized into nine EphA receptors and five EphB receptors, all of which are essential to organizing tissue in the organs of "higher organisms" (EPH Receptor Signaling and Ephrins). Extensive research has been done on both classes of Eph receptors because their influence spans a vast majority of the tissues in the body, including in neural tissue where it helps to properly guide and connect neurons during development.
In "Ephrin-A3 is required for tonotopic map precision and auditory functions in the mouse auditory brainstem," Hoshino et al. discuss their findings on the role of ligand ephrin-A3, which binds to receptor EphA3, in organizing and guiding the neurons in the mouse auditory brainstem. The main focus of this study is the formation of the tonotopic map in the cochlear nucleus of mice, where neurons corresponding to different frequencies connect to specific, corresponding locations in the cochlear nucleus. This organization allows the mouse to discriminate between sound frequencies; the tests performed on the mice were based on this hypothesis. To test the hearing threshold of Ephrin-A3 knockout mice, the researchers performed auditory brainstem response recordings where the mouse's response to sound pips at different frequencies and volumes. Then, the frequency discrimination capability of the knockout mice was tested using an acoustic startle response assay. The results showed that Ephrin-A3 plays a significant role in guiding precise tonotopic mapping in the auditory brainstem of mice, as the Ephrin-A3 knockout mice performed poorly during frequency discrimination testing. These findings are significant as they demonstrate the impact that Ephrin/Eph can have on an instrumental bodily function and show the need for further research into the impact of Ephrin/Eph throughout the body.
The relevance of studying Eph receptors becomes very clear in a recent article titled "Mass spectrometry-based proteomic platforms for better understanding of SARS-CoV-2 induced pathogenesis and potential diagnostic approaches" by Ahsan et al. where the researchers attempt to trace the pathogenesis of COVID-19 by summarizing the results of proteomic profiling. Proteomic profiling identifies the proteins involved in mechanisms of the body; the profile done in this article is specific to the mechanisms involved in the cellular response to COVID-19 infection. While many proteins across various types of tissue were identified, one of the proteins, the EphA2 receptor, "was identified by 11 studies including all proteomic platforms, suggesting it as a potential future target for SARS-CoV-2 infection mechanisms and the development of new therapeutic strategies" (Ahsan et al.). The prevalence of Eph receptors in a vast majority of tissues in the body could lead to a more comprehensive study of the pathogenesis of COVID-19 and furthermore could help millions recover from the devastating effects of the infection; this is why studying the role of Eph receptors and the ephrin ligand is essential to understanding the intricate mechanisms of the human body.
References
Lisabeth, Erika M, et al. “EPH Receptor Signaling and Ephrins.” Cold Spring Harbor Perspectives in Biology, Cold Spring Harbor Laboratory Press, 1 Sept. 2013, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753714/.
Hoshino, Natalia, et al. “Ephrin-A3 Is Required for Tonotopic Map Precision and Auditory Functions in the Mouse Auditory Brainstem.” The Journal of Comparative Neurology, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/34235739/.
Ahsan, Nagib, et al. “Mass Spectrometry‐Based Proteomic Platforms for Better Understanding of Sars‐Cov‐2 Induced Pathogenesis and Potential Diagnostic Approaches.” Analytical Science Journals, John Wiley & Sons, Ltd, 5 May 2021, https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/full/10.1002/pmic.202000279.
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