Phosphatidylserine Stimulates Ceramide 1-Phosphate (C1P) Intermembrane Transfer by C1P Transfer Proteins

  • J Biol Chem. 2017 Feb 10;292(6):2531-2541. doi: 10.1074/jbc.M116.760256.
Xiuhong Zhai  1 ,  Yong-Guang Gao  2 ,  Shrawan K Mishra  2 ,  Dhirendra K Simanshu  3 ,  Ivan A Boldyrev  4 ,  Linda M Benson  5 ,  H Robert Bergen 3rd  5 ,  Lucy Malinina  2 ,  John Mundy  6 ,  Julian G Molotkovsky  4 ,  Dinshaw J Patel  3 ,  Rhoderick E Brown  7
Affiliations
  • 1. From the Hormel Institute, University of Minnesota, Austin, Minnesota 55912, [email protected].
  • 2. From the Hormel Institute, University of Minnesota, Austin, Minnesota 55912.
  • 3. the Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065.
  • 4. the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
  • 5. the Medical Genomic Facility-Proteomics Core, Mayo Foundation, Rochester, Minnesota 55905, and.
  • 6. the Department of Biology, BioCenter, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
  • 7. From the Hormel Institute, University of Minnesota, Austin, Minnesota 55912, [email protected].
PMID: 28011644 DOI: 10.1074/jbc.M116.760256
Abstract

Genetic models for studying localized cell suicide that halt the spread of pathogen Infection and immune response activation in Plants include Arabidopsis accelerated-cell-death 11 mutant (acd11). In this mutant, sphingolipid homeostasis is disrupted via depletion of ACD11, a lipid transfer protein that is specific for ceramide 1-phosphate (C1P) and phyto-C1P. The C1P binding site in ACD11 and in human ceramide-1-phosphate transfer protein (CPTP) is surrounded by cationic residues. Here, we investigated the functional regulation of ACD11 and CPTP by anionic phosphoglycerides and found that 1-palmitoyl-2-oleoyl-phosphatidic acid or 1-palmitoyl-2-oleoyl-phosphatidylglycerol (≤15 mol %) in C1P source vesicles depressed C1P intermembrane transfer. By contrast, replacement with 1-palmitoyl-2-oleoyl-phosphatidylserine stimulated C1P transfer by ACD11 and CPTP. Notably, "soluble" phosphatidylserine (dihexanoyl-phosphatidylserine) failed to stimulate C1P transfer. Also, none of the anionic phosphoglycerides affected transfer action by human glycolipid lipid transfer protein (GLTP), which is glycolipid-specific and has few cationic residues near its glycolipid binding site. These findings provide the first evidence for a potential phosphoglyceride headgroup-specific regulatory interaction site(s) existing on the surface of any GLTP-fold and delineate new differences between GLTP superfamily members that are specific for C1P versus glycolipid.

Keywords
Arabidopsis thaliana; lipid trafficking; lipid-protein interaction; membrane biophysics; phosphatidic acid; phosphatidylglycerol; phosphatidylserine; protein-lipid interaction; sphingolipid.