GDT1/TMEM165

 

Role of TMEM165/GDT1 transporter in calcium homeostasis

In our lab, we use yeast as a model organism to understand a human disease called CDG (Congenital disorder of Glycosylation). This disease is characterized by a glycosylation defect of the secretory proteins. Some CDG-patients have a mutation in a gene called TMEM165 which is a membrane transporter localized in the Golgi apparatus. We study the yeast ortholog of TMEM165 called GDT1. We have recently demonstrated that TMEM165/GDT1 are calcium and manganese transporters. We are currently developing different strategies to further characterize the molecular function, the regulation and the structure of TMEM165/GDT1.

Figure 1 : Topology prediction of Gdt1p in the Golgi membrane. Essential residues for calcium transport are highlighted in blue.

 

Key publications :

• Demaegd et al. Newly characterized Golgi-localized family of proteins is involved in calcium and pH homeostasis in yeast and human cells. Proceedings of the National academy of sciences of the United States of America, Vol. 110, no.17, p. 6859-64 (2013). http://hdl.handle.net/2078.1/128519
• Colinet et al. Yeast Gdt1 is a Golgi-localized calcium transporter required for stress-induced calcium signaling and protein glycosylation. Scientific Reports, Vol. 6, no.24282, p. 1-11 (2016) http://hdl.handle.net/2078.1/173463
• Colinet et al. Acidic and uncharged polar residues in the consensus motifs of the yeast Ca2+ transporter Gdt1p are required for calcium transport. Cellular Microbiology, Vol. 19, no. 7, p. 1-12 (2017). http://hdl.handle.net/2078.1/180557
• Thines et al. The yeast protein Gdt1p transports Mn ions and thereby regulates manganese homeostasis in the Golgi. Journal of Biological Chemistry, Vol. 293, no. 21, p. 8048-8055 (2018). http://hdl.handle.net/2078.1/197302
• Thines et al. Yeast as a Tool for Deeper Understanding of Human Manganese-Related Diseases. Genes, Vol. 10, no.7, p. 1-17 (2019). http://hdl.handle.net/2078.1/218448