Glycosphingolipids regulate phosphatidylserine transport machinery that operates at ER-PM contact sites - PubMed
4 hours ago
- #phosphatidylserine transport
- #ER-PM contact sites
- #glycosphingolipids
- Glycosphingolipids (GSLs) like GM3 and SM4 are essential for maintaining the localization of lipid transport proteins ORP5 and ORP8 at endoplasmic reticulum-plasma membrane (ER-PM) contact sites.
- Disruption of GSL biosynthesis removes PI4-kinase Type IIIα (PI4KIIIα) and its adaptor EFR3A from the PM, lowering PM phosphatidylinositol 4-phosphate (PI4P) levels and impairing ORP5/8 function.
- ORP5 and ORP8 transport phosphatidylserine (PS) to the PM by exchanging it with PI4P, so reduced PM PI4P decreases PS content, which affects KRAS localization and signaling.
- GSLs also regulate the assembly of ER-PM membrane contact sites, impacting other machineries such as calcium release-activated calcium channels.
- This study identifies glycosphingolipids as key organizers of PS transport and ER-PM contact sites, linking lipid regulation to KRAS function.