Trpv2, also known as Transient receptor potential vanilloid type 2, is a calcium-permeable cation channel belonging to the TRPV channel family. It can be activated by heat (>52 °C), various ligands, and mechanical stresses. Under unstimulated conditions, a large portion of it is located in the endoplasmic reticulum, but upon stimulation (e.g., by phosphatidylinositol 3-kinase-activating ligands or mechanical stress), it translocates to the plasma membrane to function as a cation channel. TRPV2 is highly expressed in neurons, neuroendocrine cells, immune cells involved in innate immunity, and certain types of cancer cells, modulating various cellular functions [1].

In B cells, TRPV2-deficient mice display impaired antibody responses following immunization, indicating that TRPV2 is crucial for B cell activation and function as it contributes to membrane potential depolarization and cytoskeleton remodeling within the B cell immunological synapse [2]. In heart failure and muscular dystrophy, inactivation of TRPV2 in animal models ameliorates muscle dysgenesis, improves cardiac function, and suppresses myocardial fibrosis, suggesting TRPV2 as a potential therapeutic target [3,5]. In viral infection, Trim21-/-mice are more susceptible to HSV-1 and VSV infection, and this susceptibility is rescued by inhibition or deletion of TRPV2, demonstrating that TRIM21-mediated down-regulation of TRPV2 provides host protection against viral infections and spread [4].

In conclusion, Trpv2 plays essential roles in multiple biological processes such as B cell activation, heart function, and antiviral response. Gene-knockout mouse models have revealed its significance in these processes and in diseases like heart failure, muscular dystrophy, and viral infections, providing valuable insights for potential therapeutic strategies targeting Trpv2.

References:

1. Kojima, Itaru, Nagasawa, Masahiro. . TRPV2. In Handbook of experimental pharmacology, 222, 247-72. doi:10.1007/978-3-642-54215-2_10. https://pubmed.ncbi.nlm.nih.gov/24756709/

2. Li, Cuifeng, Zhao, Meng, Liu, Xiaohang, Li, Zhanguo, Liu, Wanli. 2024. Ion channel TRPV2 is critical in enhancing B cell activation and function. In The Journal of experimental medicine, 221, . doi:10.1084/jem.20221042. https://pubmed.ncbi.nlm.nih.gov/38353705/

3. Iwata, Yuko, Ito, Shin, Wakabayashi, Shigeo, Kitakaze, Masafumi. 2019. TRPV2 channel as a possible drug target for the treatment of heart failure. In Laboratory investigation; a journal of technical methods and pathology, 100, 207-217. doi:10.1038/s41374-019-0349-z. https://pubmed.ncbi.nlm.nih.gov/31857697/

4. Guo, Yu-Yao, Gao, Yue, Zhao, Yun-Lin, Lin, Dandan, Yao, Jing. 2024. Viral infection and spread are inhibited by the polyubiquitination and downregulation of TRPV2 channel by the interferon-stimulated gene TRIM21. In Cell reports, 43, 114095. doi:10.1016/j.celrep.2024.114095. https://pubmed.ncbi.nlm.nih.gov/38613787/

5. Iwata, Yuko, Matsumura, Tsuyoshi. 2019. Blockade of TRPV2 is a Novel Therapy for Cardiomyopathy in Muscular Dystrophy. In International journal of molecular sciences, 20, . doi:10.3390/ijms20163844. https://pubmed.ncbi.nlm.nih.gov/31394715/