Trarg1, or Trafficking regulator of GLUT4-1, is a transmembrane protein belonging to the dispanins family [2]. It positively regulates insulin-stimulated GLUT4 trafficking and insulin sensitivity, placing it within the insulin signaling network [1]. GLUT4 is crucial for glucose uptake in muscle and adipocytes, so Trarg1 is important for whole-body glucose homeostasis.

Biochemical and mass spectrometry analyses have shown that Trarg1 is dephosphorylated in response to insulin in a PI3K/Akt-dependent manner and is a substrate for GSK3 [1]. Pharmacological inhibition of GSK3 increased cell surface GLUT4 in cells stimulated with a submaximal insulin dose, and this effect was impaired following Trarg1 knockdown, suggesting that Trarg1 acts as a GSK3-mediated regulator in GLUT4 trafficking [1]. Also, in bovine fat development, miR-204 targets the 3' UTR region of the Trarg1 gene, and miR-181b and miR-204 are involved in fat development by targeting Trarg1 [3]. In laying hens, the down-regulation of Trarg1 might be the main reason for the decrease in egg-laying rate caused by maternal Escherichia coli lipopolysaccharide exposure [4]. In pigs, Trarg1 is identified as a candidate gene associated with muscle fatty acid composition and the intramuscular oleic-to-stearic fatty acid ratio [5,6].

In conclusion, Trarg1 is a key regulator in GLUT4 trafficking, which is essential for glucose homeostasis. Studies in various species have revealed its roles in different biological processes such as fat development and egg-laying rate regulation. These findings contribute to understanding the mechanisms underlying glucose metabolism, fat development, and related physiological functions in different organisms [1,3,4,5,6].

References:

1. Duan, Xiaowen, Norris, Dougall M, Humphrey, Sean J, James, David E, Fazakerley, Daniel J. . Trafficking regulator of GLUT4-1 (TRARG1) is a GSK3 substrate. In The Biochemical journal, 479, 1237-1256. doi:10.1042/BCJ20220153. https://pubmed.ncbi.nlm.nih.gov/35594055/

2. Deuis, Jennifer R, Klasfauseweh, Tabea, Walker, Lucinda, Vetter, Irina. 2024. The 'dispanins' and related proteins in physiology and neurological disease. In Trends in neurosciences, 47, 622-634. doi:10.1016/j.tins.2024.06.004. https://pubmed.ncbi.nlm.nih.gov/39025729/

3. Zhang, Sihuan, Jiang, Enhui, Kang, Zihong, Chen, Hong, Lan, Xianyong. 2022. CircRNA Profiling Reveals an Abundant circBDP1 that Regulates Bovine Fat Development by Sponging miR-181b/miR-204 Targeting Sirt1/TRARG1. In Journal of agricultural and food chemistry, 70, 14312-14328. doi:10.1021/acs.jafc.2c05939. https://pubmed.ncbi.nlm.nih.gov/36269615/

4. Liu, Lei, Wang, Wei, Adetula, Adeyinka Abiola, Yu, Ying, Chu, Qin. 2024. Effects of maternal Escherichia coli lipopolysaccharide exposure on offspring: insights from lncRNA analysis in laying hens. In Poultry science, 104, 104599. doi:10.1016/j.psj.2024.104599. https://pubmed.ncbi.nlm.nih.gov/39657467/

5. Valdés-Hernández, Jesús, Ramayo-Caldas, Yuliaxis, Passols, Magí, Sánchez, Armand, Folch, Josep M. 2023. Global analysis of the association between pig muscle fatty acid composition and gene expression using RNA-Seq. In Scientific reports, 13, 535. doi:10.1038/s41598-022-27016-x. https://pubmed.ncbi.nlm.nih.gov/36631502/

6. Valdés-Hernández, Jesús, Ramayo-Caldas, Yuliaxis, Passols, Magí, Sánchez, Armand, Folch, Josep M. 2024. Identification of differentially expressed genes and polymorphisms related to intramuscular oleic-to-stearic fatty acid ratio in pigs. In Animal genetics, 56, e13491. doi:10.1111/age.13491. https://pubmed.ncbi.nlm.nih.gov/39593270/