Deciphering the glycosylome of dystroglycanopathies using haploid screens for lassa virus entry.
Deciphering the glycosylome of dystroglycanopathies using haploid screens for lassa virus entry.
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DOI：
10.1126/science.1233675
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发表时间：
2013-04-26
期刊：
影响因子：
--
通讯作者：
Brummelkamp TR
中科院分区：
文献类型：
--
作者：
Jae LT;Raaben M;Riemersma M;van Beusekom E;Blomen VA;Velds A;Kerkhoven RM;Carette JE;Topaloglu H;Meinecke P;Wessels MW;Lefeber DJ;Whelan SP;van Bokhoven H;Brummelkamp TR
糖基化α-三聚糖聚糖（α-DG）作为多种病原体的细胞进入受体，其糖基化缺陷可导致遗传性Walker-Warburg综合征（WWS）。至少有8种蛋白对糖基酸α-DG至关重要，但许多WWS中突变的基因仍然未知。为了鉴定α-DG的修饰因子，我们对拉沙病毒进入进行了单倍体筛选，拉沙病毒是一种每年导致数千人死亡的出血热病毒，它劫持糖基化的α-DG进入细胞。在补充筛选中，我们分析了缺乏α-DG碳水化合物链或生化相关聚糖的细胞。这揭示了病毒宿主因子和一套糖基化单元，包括所有已知的Walker-Warburg基因和5个对α-DG修饰至关重要的附加因子。我们的研究结果强调了这种翻译后特征的复杂性，并指出糖营养不良症中存在基因缺陷。
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.
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影响因子：
64.8
作者：
Michele, DE;Barresi, R;Campbell, KP
通讯作者：
Campbell, KP
影响因子：
56.9
作者：
Carette, Jan E.;Guimaraes, Carla P.;Brummelkamp, Thijn R.
通讯作者：
Brummelkamp, Thijn R.
影响因子：
5.4
作者：
Kunz, S;Rojek, JM;Oldstone, MBA
通讯作者：
Oldstone, MBA
DOI：
10.1126/science.1214115
发表时间：
2012-01-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Inamori K;Yoshida-Moriguchi T;Hara Y;Anderson ME;Yu L;Campbell KP
通讯作者：
Campbell KP
影响因子：
64.8
作者：
Carette, Jan E.;Raaben, Matthijs;Wong, Anthony C.;Herbert, Andrew S.;Obernosterer, Gregor;Mulherkar, Nirupama;Kuehne, Ana I.;Kranzusch, Philip J.;Griffin, April M.;Ruthel, Gordon;Dal Cin, Paola;Dye, John M.;Whelan, Sean P.;Chandran, Kartik;Brummelkamp, Thijn R.
通讯作者：
Brummelkamp, Thijn R.