Insights into molecular and cellular functions of the Golgi calcium/manganese-proton antiporter TMEM165
Year: 2024
Type: article
Abstract: The Golgi compartment performs a number of crucial roles in the cell. However, the exact molecular mechanisms underlying these actions are not fully defined. Pathogenic mutations in genes encoding Golgi proteins may serve as an important source for expanding our knowledge. For instance, mutations in the gene encoding Transmembrane protein 165 (TMEM165) were discovered as a cause of a new type of congenital disorder of glycosylation (CDG). Comprehensive studies of TMEM165 in different model systems, including mammals, yeast, and fish uncovered the new realm of Mn 2+ homeostasis regulation. TMEM165 was shown to act as a Ca 2+ /Mn 2+ :H + antiporter in the medial- and trans-Golgi network, pumping the metal ions into the Golgi lumen and protons outside. Disruption of TMEM165 antiporter activity results in defects in N- and O-glycosylation of proteins and glycosylation of lipids. Impaired glycosylation of TMEM165-CDG arises from a lack of Mn 2+ within the Golgi. Nevertheless, Mn 2+ insufficiency in the Golgi is compensated by the activity of the ATPase SERCA2. TMEM165 turnover has also been found to be regulated by Mn 2+ cytosolic concentration. Besides causing CDG, recent investigations have demonstrated the functional involvement of TMEM165 in several other pathologies including cancer and mental health disorders. This systematic review summarizes the available information on TMEM165 molecular structure, cellular function, and its roles in health and disease.
Source: Journal of Biological Chemistry
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,800
Awards: G1000608447, G1107707869, G1196682224, G1214234794, G1218068299, Molecular regulation of skeletal muscle thermogenesis, G1413706045, G1512127578, G1530010185, Inositol 1,4,5-trisphosphate receptors and activation of cardiac fibroblasts in ischemia/reperfusion injury, G180476886, G186995139, Beta Cell Intracellular Calcium and Diabetes, Functional role of IP3 receptors in the regulation of cardiac myofibroblasts, G249311083, G2585684547, Modulation of Mitofusin Activity to Treat Heart Disease, G280444578, G281933567, G2836354684, G2940288175, A paradigm-shifting idea in storage-disease cardiomyopathy, G3074976661, G3672453180, Einstein-Montefiore Clinical and Translational Science Award Hub, G4073434654, Caspase-9 as a nodal point connecting necrotic and apoptotic cell death in myocardial infarction, Mechanisms of cardiovascular disease, G425922058, G4480573366, CTSA Administrative Supplement for Informatics Core: A novel AI/ML system to predict respiratory failure and ARDS in Covid-19 patients, G522617745, G5298350625, G531307636, G5423166509, G6133271709, G6295426566, A Novel Strategy Against Cardiotoxicity, G671159905, G6737277850, G7492960808, G7854002418, G790170206, G802470759, G8224181935, Purposeful Outreach for Diversity and Inclusion of Underrepresented in Medicine (PODIUM) Physician-Scientists, G8385843488, G8445767824, G864706750, G873634175, G9000020154, G9000036909, G9000045154, G9000045632, G9000148014, G9000203699, G9000291687, G981417163
OpenAlex ID: W4400521327