20.500.12556/RUL-182869 GD3 synthase deficiency disrupts Na[sup]+/K[sup]+ -ATPase and plasma membrane Ca[sup]2+ -ATPase function in mouse brain GD3 synthase (GD3S) is a key enzyme in the production of gangliosides, sialylated membrane glycosphingolipids with essential physiological roles in mammalian brains. To elucidate the molecular bases of neuropathological findings associated with GD3S deficiency, we performed a multilayered analysis focused on the functionality of ion transporters Na+/K+-ATPase (NKA) and plasma membrane Ca2+-ATPase (PMCA) in the cortex and cerebellum of GD3S-deficient mice (GD3S-/-). We examined global transcriptomes, NKA and PMCA gene and protein expression, the influence of membrane lipid composition on lipid raft integrity, and the activity of both ATPases, pairing them with an exploratory principal component analysis. Transcriptomic data reveal that sets of genes involved in ion transport and membrane dynamics are differentially expressed in the absence of GD3S, whereas qRT-PCR data confirm changes in gene expression of specific NKA and PMCA subunits or isoforms. Altered protein expression and significantly lower activity of both NKA and PMCA were found in the cerebral cortex of GD3S-/- mice. Analysis of membrane cholesterol content revealed segregation of cholesterol into lipid rafts, which may lead to disordered membrane lipid architecture in GD3S deficiency. Additionally, our results confirm that an imbalance in membrane ganglioside composition leads to significant alterations in ion transporters NKA and PMCA activity. Furthermore, we experimentally restored the activity of both ATPases in cortical homogenates by administering exogenous b-series gangliosides, a finding that may aid in developing therapeutic strategies targeting deficits in GD3S and other enzymes of ganglioside biosynthesis. gangliosides glycosphingolipids lipid rafts sialyltransferase St8sia1 gangliozidi glikosfingolipidi lipidni rafti St8sia1 true false true Angleški jezik Slovenski jezik Članek v reviji 2026-05-26 12:37:20 2026-05-26 12:37:28 2026-05-27 04:40:12 0000-00-00 00:00:00 2026 0 0 14 str. art. 107453 Vol. 225 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577.2 1095-953X 10.1016/j.nbd.2026.107453 279336963 RAZ_Puljko_Borna_2026.pdf RAZ_Puljko_Borna_2026.pdf 1 5869C2E88C2C5B35500493D708AD5DBC c469efd9c2c22d2b929d4a06a165cf551d467392fbe1b600884e9d90e83ff491 3e526c36-58f1-11f1-b0ab-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=234494 https://www.sciencedirect.com/science/article/pii/S0969996126001981?via%3Dihub 1 90c92e1d-58ee-11f1-b0ab-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=234493 Medicinska fakulteta 0 0 0