Tmbim4, also known as Golgi anti-apoptotic protein (GAAP) or Lifeguard 4 (Lfg4), is a highly conserved multi-transmembrane protein. It belongs to the transmembrane Bax inhibitor motif containing (TMBIM) protein family. Tmbim4 is involved in regulating intracellular Ca²⁺ levels and fluxes from the Golgi and endoplasmic reticulum, conferring resistance to apoptotic stimuli, promoting cell adhesion and migration, and playing a role in maintaining intracellular Ca²⁺ homeostasis [4,5].

In preeclampsia (PE), Tmbim4 deficiency in human trophoblast cell lines like HTR-8/SVneo impairs cell viability, migration, and invasion. It also enhances NLRP3 inflammasome activity and promotes pyroptosis, suggesting a potential role in the pathogenesis of PE [1]. In zebrafish, tmbim4 mutant embryos are more susceptible to triclocarban (TCC)-induced embryonic toxicity, with TCC exposure increasing apoptosis in the hindbrain and eyes due to abnormal autophagy regulation [2]. In lens epithelial cells, miR-125a-3p suppresses Tmbim4, leading to increased apoptosis under ultraviolet radiation B (UVB) irradiation [3].

In conclusion, Tmbim4 is crucial for maintaining normal cell function, such as cell viability, migration, and resistance to apoptosis. Gene knockout models in various organisms, like cell lines and zebrafish, have revealed its significance in diseases including preeclampsia and in response to environmental toxins. These findings highlight the potential of Tmbim4 as a therapeutic target in related disease areas.

References:

1. Chen, Yuanyao, Xiao, Lin, Sun, Guoqiang, Zhang, Huiping, Liu, Chunyan. 2023. TMBIM4 Deficiency Facilitates NLRP3 Inflammasome Activation-Induced Pyroptosis of Trophoblasts: A Potential Pathogenesis of Preeclampsia. In Biology, 12, . doi:10.3390/biology12020208. https://pubmed.ncbi.nlm.nih.gov/36829486/

2. Hu, Zhiyong, He, Liting, Wei, Jiajing, Zhang, Huiping, Liu, Chunyan. 2021. tmbim4 protects against triclocarban-induced embryonic toxicity in zebrafish by regulating autophagy and apoptosis. In Environmental pollution (Barking, Essex : 1987), 277, 116873. doi:10.1016/j.envpol.2021.116873. https://pubmed.ncbi.nlm.nih.gov/33714789/

3. Kang, Lihua, Luo, Jiawei, Li, Pengfei, Ji, Min, Guan, Huaijin. 2022. miR-125a-3p regulates apoptosis by suppressing TMBIM4 in lens epithelial cells. In International ophthalmology, 43, 1261-1274. doi:10.1007/s10792-022-02524-x. https://pubmed.ncbi.nlm.nih.gov/36173547/

4. Lisak, Dmitrij A, Schacht, Teresa, Enders, Vitalij, Bultynck, Geert, Methner, Axel. 2015. The transmembrane Bax inhibitor motif (TMBIM) containing protein family: Tissue expression, intracellular localization and effects on the ER CA²⁺-filling state. In Biochimica et biophysica acta, 1853, 2104-14. doi:10.1016/j.bbamcr.2015.03.002. https://pubmed.ncbi.nlm.nih.gov/25764978/

5. Carrara, Guia, Parsons, Maddy, Saraiva, Nuno, Smith, Geoffrey L. . Golgi anti-apoptotic protein: a tale of camels, calcium, channels and cancer. In Open biology, 7, . doi:10.1098/rsob.170045. https://pubmed.ncbi.nlm.nih.gov/28469007/