Reconstitution of phosphatidylserine transport from chemically defined donor membranes to phosphatidylserine decarboxylase 2 implicates specific lipid domains in the process.

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Wu WI, Voelker DR

Reconstitution of phosphatidylserine transport from chemically defined donor membranes to phosphatidylserine decarboxylase 2 implicates specific lipid domains in the process.

J Biol Chem. 2004 Feb 20;279(8):6635-42. Epub 2003 Dec 4.

PubMed ID

14660568 [ View in PubMed

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Abstract

Phosphatidylserine (PtdSer) is transported from its site of synthesis in the endoplasmic reticulum to the locus of PtdSer decarboxylase 2 (Psd2p) in the Golgi/vacuole and decarboxylated to form phosphatidylethanolamine. Recent biochemical and genetic evidence has implicated the C2 domain of Psd2p and a membrane-bound form of the phosphatidylinositol binding/transfer protein, PstB2p, as essential for this transport process. We devised a reconstituted system in which chemically defined donor membranes function to transfer PtdSer to the biological acceptor membranes containing Psd2p. The transfer of PtdSer is poor when the donor membranes have a high degree of curvature but markedly enhanced when the membranes are relatively planar (> or =400-nm diameter). PtdSer transfer is also dependent upon both the bulk and the surface concentrations of the lipid, with pure PtdSer vesicles acting as the most efficient donors at all concentrations. The lipid transfer from donor membranes containing either 100% PtdSer or 50% PtdSer at a fixed concentration (e.g. 250 microM PtdSer) differs by a factor of 20. Surface dilution of PtdSer by choline, ethanolamine, glycerol, and inositol phospholipids markedly inhibits PtdSer transfer, whereas phosphatidic acid (PtdOH) stimulates the transfer. Most importantly, the transfer of PtdSer from liposomes to Psd2p fails to occur in acceptor membranes from strains lacking PstB2p or the C2 domain of Psd2p. These data support a model for PtdSer transport from planar domains highly enriched in PtdSer or in PtdSer plus PtdOH.

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Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Phosphatidyl serine	Phosphatidylserine decarboxylase proenzyme	Protein	Humans	Unknown	Not Available	Details