What makes Phosphatidylserine a Novel Regulator of Ceramide‐1‐Phosphate Transfer Proteins?

Abstract

The Arabidopsis accelerated-cell-death11 (acd11) mutant provides a genetic model for studying localized cell suicide to halt the spread of pathogen infection in plants. Recently, we showed that ACD11 functions as a lipid transfer protein for ceramide-1-phosphate (C1P) and phyto-C1P but forms a GLTP-fold. Here, we have investigated how various negatively-charged (anionic) phospholipids affect C1P intermembrane transfer by ACD11 and CPTP using Förster resonance energy transfer involving anthrylvinyl and perylenoyl lipid probes. The anionic phospholipids mixed in combination POPC were phosphatidylserine (PS), phosphatidic acid (PA), and phosphatidyl­glycerol (PG) as well as zwitterionic phosphatidyl­ethanol­amine (PE). With ACD11, including POPS (蠄 15 mole%) in POPC vesicles increased C1P transfer while PA & PG decreased C1P transfer. Notably, 'soluble'-PS (di-6:0-PS) failed to stimu­late C1P transfer. Combining POPS with di-6:0-PS mitigated the POPS stimula­tory effect. With glycolipid-specific GLTP, all three anionic lipids decreased SL transfer. Structural analyses of the putative membrane domain of ACD11 involving modeled interactions with soluble PS have identified a potential PS membrane docking site that regulates ACD11 activity.[Support: NIGMS GM45928 & NCI CA121493, Danish Strategic Res Council 09-067148, Russian Fdn Basic Res 012-04-00168; Abby Rockefeller Mauze Trust, Maloris & Hormel Fnds.]