Kremen1 is a transmembrane receptor that plays diverse and crucial roles in biological processes. It is involved in the regulation of Wnt signaling, and acts as a dependence receptor, triggering cell death unless bound to its ligand Dickkopf1 [2,5]. Kremen1 also has significance in the context of virus-host interactions and mechanosensory hair cell development [1,3,4,6,7].

In virus-host interactions, Kremen1 has been identified as an alternative functional receptor for SARS-CoV-2, enabling the virus to enter cells independently of ACE2 [1]. It is also a host entry receptor for a major group of Enteroviruses, like coxsackievirus A10. Loss of Kremen1 renders cells resistant to CV-A10 infection, and Kremen-deficient mice are resistant to CV-A10-induced lethal paralysis, highlighting its importance in viral infections [3]. In the development and regeneration of mechanosensory hair cells, Kremen1 inhibits Wnt signaling and hair cell formation. In zebrafish, overactive Wnt signaling in kremen1 mutant lines leads to excessive regeneration of support cells and hair cells without increased proliferation [4,7]. In the mammalian cochlea, Kremen1 biases cells towards supporting cell fate and suppresses hair cell formation [6].

In conclusion, Kremen1 is a multifunctional gene involved in cell survival, virus-host interactions, and the development and regeneration of mechanosensory hair cells. The use of gene knockout models, such as Kremen-deficient mice, has been instrumental in revealing its role in viral infections and hair cell-related processes, providing potential insights into disease mechanisms and therapeutic strategies.

References:

1. Gu, Yunqing, Cao, Jun, Zhang, Xinyu, Luo, Min, Lu, Zhigang. 2021. Receptome profiling identifies KREMEN1 and ASGR1 as alternative functional receptors of SARS-CoV-2. In Cell research, 32, 24-37. doi:10.1038/s41422-021-00595-6. https://pubmed.ncbi.nlm.nih.gov/34837059/

2. Sumia, Iffat, Pierani, Alessandra, Causeret, Frédéric. 2019. Kremen1-induced cell death is regulated by homo- and heterodimerization. In Cell death discovery, 5, 91. doi:10.1038/s41420-019-0175-5. https://pubmed.ncbi.nlm.nih.gov/31069116/

3. Staring, Jacqueline, van den Hengel, Lisa G, Raaben, Matthijs, Carette, Jan E, Brummelkamp, Thijn R. 2018. KREMEN1 Is a Host Entry Receptor for a Major Group of Enteroviruses. In Cell host & microbe, 23, 636-643.e5. doi:10.1016/j.chom.2018.03.019. https://pubmed.ncbi.nlm.nih.gov/29681460/

4. Megerson, Ellen, Kuehn, Michael, Leifer, Ben, Bell, Jon, McGraw, Hillary F. 2023. Kremen1 regulates the regenerative capacity of support cells and mechanosensory hair cells in the zebrafish lateral line. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.07.27.550825. https://pubmed.ncbi.nlm.nih.gov/37546780/

5. Causeret, F, Sumia, I, Pierani, A. 2015. Kremen1 and Dickkopf1 control cell survival in a Wnt-independent manner. In Cell death and differentiation, 23, 323-32. doi:10.1038/cdd.2015.100. https://pubmed.ncbi.nlm.nih.gov/26206087/

6. Mulvaney, Joanna F, Thompkins, Cathrine, Noda, Teppei, Coffin, Allison, Dabdoub, Alain. 2016. Kremen1 regulates mechanosensory hair cell development in the mammalian cochlea and the zebrafish lateral line. In Scientific reports, 6, 31668. doi:10.1038/srep31668. https://pubmed.ncbi.nlm.nih.gov/27550540/

7. Megerson, Ellen, Kuehn, Michael, Leifer, Ben, Snyder, Julia L, McGraw, Hillary F. 2023. Kremen1 regulates the regenerative capacity of support cells and mechanosensory hair cells in the zebrafish lateral line. In iScience, 27, 108678. doi:10.1016/j.isci.2023.108678. https://pubmed.ncbi.nlm.nih.gov/38205258/