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Cell Rep. 2015 Jun 23;11(11):1727-36. doi: 10.1016/j.celrep.2015.05.026. Epub 2015 Jun 11.

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

Author information

1
Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, CO 80309, USA.
2
Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
3
Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, CO 80309, USA.
4
Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, CO 80309, USA. Electronic address: jingshi.shen@colorado.edu.

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.

PMID:
26074080
PMCID:
PMC4481156
DOI:
10.1016/j.celrep.2015.05.026
[Indexed for MEDLINE]
Free PMC Article

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