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  • Deciphering the Glycosylome...
    Jae, Lucas T.; Raaben, Matthijs; Riemersma, Moniek; van Beusekom, Ellen; Blomen, Vincent A.; Velds, Arno; Kerkhoven, Ron. M.; Carette, Jan E.; Topaloglu, Haluk; Meinecke, Peter; Wessels, Marja W.; Lefeber, Dirk J.; Whelan, Sean P.; van Bokhoven, Hans; Brummelkamp, Thijn R.

    Science, 04/2013, Letnik: 340, Številka: 6131
    Journal Article

    Glycosylated α-dystroglycan (α-DG) serves as cellular entry receptor for multiple pathogens, and defects in its glycosylation cause hereditary Walker-Warburg syndrome (WWS). At least eight proteins are critical to glycosylate α-DG, but many genes mutated in WWS remain unknown. To identify modifiers of α-DG, we performed a haploid screen for Lassa virus entry, a hemorrhagic fever virus causing thousands of deaths annually that hijacks glycosylated α-DG to enter cells. In complementary screens, we profiled cells for absence of α-DG carbohydrate chains or biochemically related glycans. This revealed virus host factors and a suite of glycosylation units, including all known Walker-Warburg genes and five additional factors critical for the modification of α-DG. Our findings accentuate the complexity of this posttranslational feature and point out genes defective in dystroglycanopathies.