Deciphering the Glycosylome of Dystroglycanopathies Using Haploid Screens for Lassa Virus Entry

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Jae L. T., Raaben M., Riemersma M., van Beusekom E., Blomen V. A., Velds A., ...Daha Fazla

SCIENCE, cilt.340, sa.6131, ss.479-483, 2013 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 340 Sayı: 6131
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1126/science.1233675
  • Dergi Adı: SCIENCE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.479-483
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Glycosylated alpha-dystroglycan (alpha-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 alpha-DG, but many genes mutated in WWS remain unknown. To identify modifiers of alpha-DG, we performed a haploid screen for Lassa virus entry, a hemorrhagic fever virus causing thousands of deaths annually that hijacks glycosylated alpha-DG to enter cells. In complementary screens, we profiled cells for absence of alpha-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 alpha-DG. Our findings accentuate the complexity of this posttranslational feature and point out genes defective in dystroglycanopathies.