GNAT3, also known as gustducin, is the α subunit of a G-protein that governs sweet, savory, and bitter taste transduction pathways [3]. It is involved in chemosensory signaling and plays a significant role in maintaining tissue homeostasis in various non-gustatory tissues as well as in taste-related functions [2,3]. Genetic models, such as gene-knockout (KO) mouse models, have been crucial in studying its functions.

In pancreatic cancer, Gnat3-null (Gnat3-/-) mice crossed with KC mice showed that ablation of Gnat3 increased the release of tumor-promoting cytokines like CXCL1 and CXCL2 in organoid conditioned media. In Gnat3-/-;KCERT pancreata, there were altered expression of immunomodulatory genes in Cxcr2-expressing myeloid-derived suppressor cells (MDSCs) and an increased number of granulocytic MDSCs. Aged Gnat3-/-;KC mice progressed more rapidly to metastatic carcinoma compared with KC controls, indicating that Gnat3 suppresses pancreatic cancer progression [1]. In periodontitis, Gnat3-/-mice abolished the anti-inflammatory effects of salicin, which activates Tas2r143-mediated bitter taste signaling in gingival fibroblasts to alleviate periodontitis, suggesting Gnat3's role in periodontal homeostasis [2].

In conclusion, GNAT3 is essential for chemosensory signaling in taste perception and tissue homeostasis. Studies using Gnat3 KO mouse models have revealed its significance in pancreatic cancer progression and periodontitis, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Hoffman, Megan T, Kemp, Samantha B, Salas-Escabillas, Daniel J, Wen, Hui-Ju, Crawford, Howard C. 2020. The Gustatory Sensory G-Protein GNAT3 Suppresses Pancreatic Cancer Progression in Mice. In Cellular and molecular gastroenterology and hepatology, 11, 349-369. doi:10.1016/j.jcmgh.2020.08.011. https://pubmed.ncbi.nlm.nih.gov/32882403/

2. Zhang, Zhiying, Zhou, Zhiyan, Liu, Jiaxin, Zheng, Xin, Xu, Xin. 2024. Salicin alleviates periodontitis via Tas2r143/gustducin signaling in fibroblasts. In Frontiers in immunology, 15, 1374900. doi:10.3389/fimmu.2024.1374900. https://pubmed.ncbi.nlm.nih.gov/38605968/

3. Wooding, Stephen P, Ramirez, Vicente A. . Worldwide diversity, association potential, and natural selection in the superimposed taste genes, CD36 and GNAT3. In Chemical senses, 47, . doi:10.1093/chemse/bjab052. https://pubmed.ncbi.nlm.nih.gov/34972209/