1,10-Phenanthroline inhibits glycosylphosphatidylinositol anchoring by preventing phosphoethanolamine addition to glycosylphosphatidylinositol anchor precursors

K. J. Mann, D. Sevlever

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

The glycosylphosphatidylinositol (GPI) moiety is widely used to anchor a functionally diverse group of proteins to the plasma membrane of eukaryotes. In mammals, the predominant glycan structure of the GPI anchor consists of EthN-P-Man-Man-(EthN-P)Man-GlcN attached to an inositol phospholipid. In a smaller percentage of anchors analyzed to date, a third P-EthN group linked to the middle mannosyl residue was found. The transfer of the three P-EthN groups present in the GPI glycan core is likely to be carded out by three different GPI-phosphoethanolamine transferases (GPI-PETs). Here we report that 1,10-phenanthroline (PNT), a commonly used inhibitor of metalloproteases, is a novel inhibitor of GPI anchor synthesis. Addition of PNT to cells caused the accumulation of GPI anchor intermediates that are substrates for GPI-PETs, suggesting that these enzymes are the targets of PNT. ZnCl2 blocked the effect of PNT, a known Zn chelator, and Zn itself was able to stimulate the GPI anchor synthesis, indicating that this cation is likely to be required for GPI-PET activity. PNT acutely inhibited the synthesis of GPI-anchored proteins, but the synthesis was rapidly restored once the inhibitor was washed out. Therefore, PNT will be a useful tool to study the metabolism and trafficking of GPI anchor intermediates by providing a switch to turn the pathway on and off.

Original languageEnglish (US)
Pages (from-to)1205-1213
Number of pages9
JournalBiochemistry
Volume40
Issue number5
DOIs
StatePublished - Feb 6 2001

ASJC Scopus subject areas

  • Biochemistry

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