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


Authors: Zhai, X.; Gao, Y. G.; Mishra, S. K.; Simanshu, D. K.; Boldyrev, I. A.; Benson, L. M.; Bergen, H. R. 3rd; Malinina, L.; Mundy, J.; Molotkovsky, J. G.; Patel, D. J.; Brown, R. E.
Article Title: Phosphatidylserine stimulates ceramide 1-phosphate (C1P) intermembrane transfer by C1P transfer proteins
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. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Keywords: proteins; cell death; ceramides; intermembrane transfer; lipid transfer protein; phosphatidylserine; pathogen infection; bins; ceramide 1-phosphate; functional regulation; phosphate transfer; regulatory interactions
Journal Title: Journal of Biological Chemistry
Volume: 292
Issue: 6
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2017-02-10
Start Page: 2531
End Page: 2541
Language: English
DOI: 10.1074/jbc.M116.760256
PROVIDER: scopus
PMCID: PMC5313119
PUBMED: 28011644
DOI/URL:
Notes: Article -- Export Date: 2 March 2017 -- Source: Scopus
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  1. Dinshaw J Patel
    478 Patel