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. Epub 2016 Dec 23.

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.

MeSH terms

  • Apoptosis Regulatory Proteins / chemistry
  • Apoptosis Regulatory Proteins / metabolism
  • Arabidopsis Proteins / chemistry
  • Arabidopsis Proteins / metabolism
  • Biological Transport
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Line
  • Ceramides / metabolism*
  • Crystallography, X-Ray
  • Humans
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / metabolism
  • Phosphatidylserines / physiology*
  • Phospholipid Transfer Proteins
  • Protein Binding
  • Static Electricity

Substances

  • ACD11 protein, Arabidopsis
  • Apoptosis Regulatory Proteins
  • Arabidopsis Proteins
  • CPTP protein, human
  • Carrier Proteins
  • Ceramides
  • Membrane Transport Proteins
  • Phosphatidylserines
  • Phospholipid Transfer Proteins
  • ceramide 1-phosphate

Associated data

  • PDB/4NTI