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.

dx.doi.org/10.1126/science.1233675, hdl.handle.net/1765/40191
Science
Erasmus MC: University Medical Center Rotterdam

Jae, L.T, Raaben, M, Riemersma, M, van Beusekom, E, Blomen, V.A, Velds, A, … Brummelkamp, T.R. (2013). Deciphering the glycosylome of dystroglycanopathies using haploid screens for Lassa virus entry. Science, 340(6131), 479–483. doi:10.1126/science.1233675