Human Smp3p adds a fourth mannose to yeast and human glycosylphosphatidylinositol precursors in vivo

Barbara W. Taron, Paul A. Colussi, Jill M. Wiedman, Peter Orlean, Christopher H. Taron

Research output: Contribution to journalArticle

Abstract

Yeast and human glycosylphosphatidylinositol (GPI) precursors differ in the extent to which a fourth mannose is present as a side branch of the third core mannose. A fourth mannose addition to GPIs has scarcely been detected in studies of mammalian GPI synthesis but is an essential step in the Saccharomyces cerevisiae pathway. We report that human SMP3 encodes a functional homolog of the yeast Smp3 GPI fourth mannosyltransferase. Expression of hSMP3 in yeast complements growth and biochemical defects of smp3 mutants and permits in vivo mannosylation of trimannosyl (Man3)-GPIs. Immunolocalization shows that hSmp3p resides in the endoplasmic reticulum in human cells. Northern analysis of mRNA from human tissues and cell lines indicates that hSMP3 is expressed in most tissues, with the highest levels in brain and colon, but its mRNA is nearly absent from cultured human cell lines. Correspondingly, increasing expression of hSMP3 in cultured HeLa cells causes abundant formation of three putative tetramannosyl (Man4)-GPIs. Our data indicate that hSmp3p functions as a mannosyltransferase that adds a fourth mannose to certain Man3-GPIs during biosynthesis of the human GPI precursor, and suggest it may do so in a tissue-specific manner.

Original languageEnglish (US)
Pages (from-to)36083-36092
Number of pages10
JournalJournal of Biological Chemistry
Volume279
Issue number34
DOIs
StatePublished - Aug 20 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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