Phosphatidylserine stimulates ceramide 1-phosphate (C1P) intermembrane transfer by C1P transfer proteins

Xiuhong Zhai, Yong Guang Gao, Shrawan K. Mishra, Dhirendra K. Simanshu, Ivan A. Boldyrev, Linda M. Benson, H. Robert Bergen, Lucy Malinina, John Mundy, Julian G. Molotkovsky, Dinshaw J. Patel, Rhoderick E. Brown

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2531-2541
Number of pages11
JournalJournal of Biological Chemistry
Issue number6
StatePublished - Feb 10 2017

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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