Trpc3, a member of the mammalian transient receptor potential (TRP) superfamily of ion channels, is a Ca2+-permeable non-selective cation channel [2]. It is ubiquitously expressed and controls functions in the cardiovascular system, brain, immunity, cancer, and tissue remodeling. TRPC3 can be activated by diacylglycerols (DAG), G-protein coupled receptors (GPCR), and mechanical distortion of the plasma membrane, and is involved in various signaling processes [2,3].

In stress-induced senescent fibroblasts, TRPC3 protein is down-regulated regardless of the senescence inducer. This down-regulation promotes cytosolic/mitochondrial Ca2+ oscillations, elevates mitochondrial Ca2+ load, mitochondrial oxygen consumption rate, and oxidative phosphorylation. Re-expression of TRPC3 in senescent cells diminishes mitochondrial Ca2+ load and promotes escape from OIS-induced senescence. Cellular senescence evoked by TRPC3 down-regulation in stromal cells displays a pro-inflammatory and tumour-promoting secretome that encourages cancer epithelial cell proliferation and tumour growth in vivo [1]. In Trpc3-/-mice, there is defective insulin secretion and glucose intolerance, indicating that TRPC3 is a critical regulator of insulin secretion and glucose control [4].

In conclusion, Trpc3 plays essential roles in multiple biological processes. Its down-regulation in senescent cells promotes tumour-promoting senescence, and its deficiency in mice leads to abnormal insulin secretion and glucose intolerance. These findings from model-based research, especially the use of knockout mouse models, enhance our understanding of the role of Trpc3 in cancer and diabetes, providing potential targets for therapeutic interventions.

References:

1. Farfariello, Valerio, Gordienko, Dmitri V, Mesilmany, Lina, Lemonnier, Loïc, Prevarskaya, Natalia. 2022. TRPC3 shapes the ER-mitochondria Ca2+ transfer characterizing tumour-promoting senescence. In Nature communications, 13, 956. doi:10.1038/s41467-022-28597-x. https://pubmed.ncbi.nlm.nih.gov/35177596/

2. Tiapko, Oleksandra, Groschner, Klaus. 2018. TRPC3 as a Target of Novel Therapeutic Interventions. In Cells, 7, . doi:10.3390/cells7070083. https://pubmed.ncbi.nlm.nih.gov/30037143/

3. Khayyat, Naghmeh Hassanzadeh, Tomilin, Viktor N, Zaika, Oleg, Pochynyuk, Oleh. . Polymodal roles of TRPC3 channel in the kidney. In Channels (Austin, Tex.), 14, 257-267. doi:10.1080/19336950.2020.1804153. https://pubmed.ncbi.nlm.nih.gov/32787494/

4. Rached, Gaëlle, Saliba, Youakim, Maddah, Dina, Birnbaumer, Lutz, Fares, Nassim. 2023. TRPC3 Regulates Islet Beta-Cell Insulin Secretion. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2204846. doi:10.1002/advs.202204846. https://pubmed.ncbi.nlm.nih.gov/36642838/