title: Deciphering the glycosylome of dystroglycanopathies using haploid screens for lassa virus entry.
abstract: 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.
authors.affiliation: Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, Netherlands.
authors.forename: Lucas T
authors.initials: LT
authors.lastname: Jae
authors.forename: Matthijs
authors.initials: M
authors.lastname: Raaben
authors.forename: Moniek
authors.initials: M
authors.lastname: Riemersma
authors.forename: Ellen
authors.initials: E
authors.lastname: van Beusekom
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Blomen
authors.forename: Arno
authors.initials: A
authors.lastname: Velds
authors.forename: Ron M
authors.initials: RM
authors.lastname: Kerkhoven
authors.forename: Jan E
authors.initials: JE
authors.lastname: Carette
authors.forename: Haluk
authors.initials: H
authors.lastname: Topaloglu
authors.forename: Peter
authors.initials: P
authors.lastname: Meinecke
authors.forename: Marja W
authors.initials: MW
authors.lastname: Wessels
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Lefeber
authors.forename: Sean P
authors.initials: SP
authors.lastname: Whelan
authors.forename: Hans
authors.initials: H
authors.lastname: van Bokhoven
authors.forename: Thijn R
authors.initials: TR
authors.lastname: Brummelkamp
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D049030:Dystroglycans / Q000378:metabolism*; D005260:Female; D006031:Glycosylation; D006238:Haploidy; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D007223:Infant; D007835:Lassa Fever / Q000235:genetics* / Q000821:virology; D007836:Lassa virus / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010430:Pentosyltransferases; D020543:Proteome / Q000378:metabolism*; D053586:Virus Internalization; D058494:Walker-Warburg Syndrome / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D020543:Proteome; D049030:Dystroglycans; D010430:Pentosyltransferases; C578283:RXYLT1 protein, human