Comparative Haploid Genetic Screens Reveal Divergent Pathways in the Biogenesis and Trafficking of Glycophosphatidylinositol-Anchored Proteins

Eric M. Davis, Jihye Kim, Bridget L. Menasche, Jacob Sheppard, Xuedong Liu, Aik-Choon Tan, Jingshi Shen

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Glycophosphatidylinositol-anchored proteins (GPI-APs) play essential roles in physiology, but their biogenesis and trafficking have not been systematically characterized. Here, we took advantage of the recently available haploid genetics approach to dissect GPI-AP pathways in human cells using prion protein (PrP) and CD59 as model molecules. Our screens recovered a large number of common and unexpectedly specialized factors in the GPI-AP pathways. PIGN, PGAP2, and PIGF, which encode GPI anchor-modifying enzymes, were selectively isolated in the CD59 screen, suggesting that GPI anchor composition significantly influences the biogenesis of GPI-APs in a substrate-dependent manner. SEC62 and SEC63, which encode components of the ER-targeting machinery, were selectively recovered in the PrP screen, indicating that they do not constitute a universal route for the biogenesis of mammalian GPI-APs. Together, these comparative haploid genetic screens demonstrate that, despite their similarity in overall architecture and subcellular localization, GPI-APs follow markedly distinct biosynthetic and trafficking pathways. Using comparative haploid genetic screens in human cells, Davis et al. find that GPI-anchored proteins follow markedly distinct biosynthetic and trafficking pathways in spite of their similarity in overall architecture and subcellular localization.

Original languageEnglish
Pages (from-to)1727-1736
Number of pages10
JournalCell Reports
Volume11
Issue number11
DOIs
Publication statusPublished - 2015 Jun 23
Externally publishedYes

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Haploidy
Proteins
Biosynthetic Pathways
Anchors
Cells
Physiology
Machinery
Molecules
Substrates
Enzymes
Chemical analysis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Comparative Haploid Genetic Screens Reveal Divergent Pathways in the Biogenesis and Trafficking of Glycophosphatidylinositol-Anchored Proteins. / Davis, Eric M.; Kim, Jihye; Menasche, Bridget L.; Sheppard, Jacob; Liu, Xuedong; Tan, Aik-Choon; Shen, Jingshi.

In: Cell Reports, Vol. 11, No. 11, 23.06.2015, p. 1727-1736.

Research output: Contribution to journalArticle

Davis, Eric M. ; Kim, Jihye ; Menasche, Bridget L. ; Sheppard, Jacob ; Liu, Xuedong ; Tan, Aik-Choon ; Shen, Jingshi. / Comparative Haploid Genetic Screens Reveal Divergent Pathways in the Biogenesis and Trafficking of Glycophosphatidylinositol-Anchored Proteins. In: Cell Reports. 2015 ; Vol. 11, No. 11. pp. 1727-1736.
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