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1.A.119 The Stress-inducible Transmembrane Protein, TMPIT1, TACAN or TMEM120A (TMPIT1) Family

A drought stress-inducible putative membrane protein was cloned from root tissue of wild emmer wheat. TMPIT1, is a member of the widespread but uncharacterised TMPIT (transmembrane protein inducible by TNF-α) family. The TdicTMPIT1 gene is upregulated on drought stress in drought-tolerant wild emmer wheat, but not in a drought-sensitive accession or in cultivated durum wheat. The TdicTMPIT1 product is a membrane protein with four transmembrane helices. 

Human Tmem120A and Tmem120B, nuclear membrane proteins, are found in fat cells, and both are induced during 3T3-L1 adipocyte differentiation. Knockdown of one or the other protein alters expression of several genes required for adipocyte differentiation. The double knockdown increased the strength of the effects, reducing, for example, Glut4 levels by 95% upon pharmacologically induced differentiation. The TMEM120A and B fat-specific nuclear envelope transmembrane proteins may play a contributory role in the tissue-specific pathologies (Batrakou et al. 2015).

Mechanotransduction, the conversion of mechanical stimuli into electrical signals, is a fundamental process underlying essential physiological functions such as touch and pain sensing, hearing, and proprioception. Beaulieu-Laroche et al. 2020 reported the identification of TACAN (Tmem120A), an ion channel involved in sensing mechanical pain. TACAN is expressed in a subset of nociceptors, and its heterologous expression increases mechanically evoked currents in cell lines. Purification and reconstitution of TACAN in synthetic lipids generates a functional ion channel. A nociceptor-specific inducible knockout of TACAN decreases the mechanosensitivity of nociceptors and reduces behavioral responses to painful mechanical stimuli but not to thermal or touch stimuli. Beaulieu-Laroche et al. 2020 proposed that TACAN is an ion channel that contributes to sensing mechanical pain.

The generalized transport reaction catalyzed by members of the TMPIT family is:

ions (out) ⇋ ions (in)

References associated with 1.A.119 family:

Beaulieu-Laroche, L., M. Christin, A. Donoghue, F. Agosti, N. Yousefpour, H. Petitjean, A. Davidova, C. Stanton, U. Khan, C. Dietz, E. Faure, T. Fatima, A. MacPherson, S. Mouchbahani-Constance, D.G. Bisson, L. Haglund, J.A. Ouellet, L.S. Stone, J. Samson, M.J. Smith, K. Ask, A. Ribeiro-da-Silva, R. Blunck, K. Poole, E. Bourinet, and R. Sharif-Naeini. (2020). TACAN Is an Ion Channel Involved in Sensing Mechanical Pain. Cell 180: 956-967.e17. 32084332
Chen, X., Y. Wang, Y. Li, X. Lu, J. Chen, M. Li, T. Wen, N. Liu, S. Chang, X. Zhang, X. Yang, and Y. Shen. (2022). Cryo-EM structure of the human TACAN in a closed state. Cell Rep 38: 110445. 35235791
Czapiewski, R., D.G. Batrakou, J.I. de Las Heras, R.N. Carter, A. Sivakumar, M. Sliwinska, C.R. Dixon, S. Webb, G. Lattanzi, N.M. Morton, and E.C. Schirmer. (2022). Genomic loci mispositioning in Tmem120a knockout mice yields latent lipodystrophy. Nat Commun 13: 321. 35027552
Gabrielle, M. and T. Rohacs. (2023). TMEM120A/TACAN: A putative regulator of ion channels, mechanosensation, and lipid metabolism. Channels (Austin) 17: 2237306. 37523628
Niu, Y., X. Tao, G. Vaisey, P.D.B. Olinares, H. Alwaseem, B.T. Chait, and R. MacKinnon. (2021). Analysis of the mechanosensor channel functionality of TACAN. Elife 10:. 34374644
Qian, N., S. Li, and X. Tan. (2022). The curious case of TMEM120A: Mechanosensor, fat regulator, or antiviral defender? Bioessays 44: e2200045. 35419854
Rong, Y., J. Jiang, Y. Gao, J. Guo, D. Song, W. Liu, M. Zhang, Y. Zhao, B. Xiao, and Z. Liu. (2021). TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells. Elife 10:. [Epub: Ahead of Print] 34409941
Xue, J., Y. Han, H. Baniasadi, W. Zeng, J. Pei, N.V. Grishin, J. Wang, B.P. Tu, and Y. Jiang. (2021). TMEM120A is a coenzyme A-binding membrane protein with structural similarities to ELOVL fatty acid elongase. Elife 10:. 34374645