Calhm6, also known as FAM26F, is a calcium homeostasis modulator ion channel [2,4]. It is crucial for regulating the early innate control of Listeria monocytogenes infection in vivo. In the immune system, it promotes cell-cell crosstalk at the immunological synapse via ATP release, fine-tuning the timing of innate immune responses [1]. It is also associated with the regulation of the immune response, which may be related to the pathogenesis of diseases such as steroid-sensitive nephrotic syndrome (SSNS) [3,5].

A study generating Calhm6-/-mice reported that CALHM6 is upregulated in macrophages by pathogen-derived signals, relocates to the macrophage-NK cell synapse, facilitating ATP release and controlling NK cell activation kinetics [1]. In the context of SSNS, GWAS identified a locus containing CALHM6, with the risk allele associated with lower lymphocytic expression of CALHM6, potentially explaining the disease's infection-triggered onset [5].

In summary, Calhm6 is essential for the regulation of innate immune responses, especially in controlling bacterial infections. The use of Calhm6-/-mouse models has provided insights into its role in the immune synapse and the potential link between Calhm6 and diseases like SSNS, highlighting its significance in understanding the immune-related disease mechanisms [1,5].

References:

1. Danielli, Sara, Ma, Zhongming, Pantazi, Eirini, Foskett, J Kevin, Bezbradica, Jelena S. 2023. The ion channel CALHM6 controls bacterial infection-induced cellular cross-talk at the immunological synapse. In The EMBO journal, 42, e111450. doi:10.15252/embj.2022111450. https://pubmed.ncbi.nlm.nih.gov/36861806/

2. Javed, Aneela, Habib, Sabahat, Ayub, Aaima. 2024. Evolution of protein domain repertoires of CALHM6. In PeerJ, 12, e16063. doi:10.7717/peerj.16063. https://pubmed.ncbi.nlm.nih.gov/38188152/

3. Horinouchi, Tomoko, Nozu, Kandai, Iijima, Kazumoto. 2022. An updated view of the pathogenesis of steroid-sensitive nephrotic syndrome. In Pediatric nephrology (Berlin, Germany), 37, 1957-1965. doi:10.1007/s00467-021-05401-4. https://pubmed.ncbi.nlm.nih.gov/35006356/

4. Jabeen, Kehkshan, Malik, Uzma, Mansoor, Sajid, Zahid, Saadia, Javed, Aneela. 2021. Effect of oxidative stress and calcium deregulation on FAM26F (CALHM6) expression during hepatitis B virus infection. In BMC infectious diseases, 21, 228. doi:10.1186/s12879-021-05888-0. https://pubmed.ncbi.nlm.nih.gov/33639860/

5. Dufek, Stephanie, Cheshire, Chris, Levine, Adam P, Kleta, Robert, Bockenhauer, Detlef. 2019. Genetic Identification of Two Novel Loci Associated with Steroid-Sensitive Nephrotic Syndrome. In Journal of the American Society of Nephrology : JASN, 30, 1375-1384. doi:10.1681/ASN.2018101054. https://pubmed.ncbi.nlm.nih.gov/31263063/