Heparan sulfate proteoglycans (HSPGs) and chondroitin sulfate proteoglycans (CSPGs) function as endocytic receptors for an internalizing anti-nucleic acid antibody.
Heparan sulfate proteoglycans (HSPGs) and chondroitin sulfate proteoglycans (CSPGs) function as endocytic receptors for an internalizing anti-nucleic acid antibody.
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DOI：
10.1038/s41598-017-14793-z
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发表时间：
2017-10-30
影响因子：
4.6
通讯作者：
Kwon MH
中科院分区：
文献类型：
--
作者：
Park H;Kim M;Kim HJ;Lee Y;Seo Y;Pham CD;Lee J;Byun SJ;Kwon MH
单克隆抗DNA自身抗体的一个子集进入各种活细胞。在这里，我们的目的是确定内吞受体的内化抗核酸自身抗体，3D 8单链可变片段（scFv）。我们发现，在可溶性硫酸乙酰肝素（HS）/硫酸软骨素（CS）缺陷或去除的细胞中以及在可溶性HS和CS存在的情况下，3D 8 scFv的细胞表面结合和内化被显着抑制。3D 8 scFv在HeLa细胞中与HS蛋白聚糖（HSPG）或CSPG共定位于细胞内。3D 8 scFv与代表性的单个HSPG和CSPG分子共内吞和共沉淀：多配体蛋白聚糖-2（跨膜HSPG）、磷脂酰肌醇蛋白聚糖-3（糖基磷脂酰肌醇（GPI）锚定的HSPG）; CD 44（跨膜CSPG）;和短蛋白聚糖（GPI锚定的CSPG）。收集的数据表明，3D 8 scFv与HSPG和CSPG的带负电荷的糖链结合，然后与这些分子一起沿着内化，而不管这些蛋白聚糖如何与细胞膜结合。这是第一项研究表明，抗DNA抗体通过HSPG和CSPG同时进入细胞。这些数据可能有助于了解结合抗DNA自身抗体的内吞受体。该研究还提供了对大分子递送的潜在细胞膜靶点的深入了解。
A subset of monoclonal anti-DNA autoantibodies enters a variety of living cells. Here, we aimed to identify the endocytic receptors recognized by an internalizing anti-nucleic acid autoantibody, the 3D8 single-chain variable fragment (scFv). We found that cell surface binding and internalization of 3D8 scFv were inhibited markedly in soluble heparan sulfate (HS)/chondroitin sulfate (CS)-deficient or -removed cells and in the presence of soluble HS and CS. 3D8 scFv colocalized intracellularly with either HS proteoglycans (HSPGs) or CSPGs in HeLa cells. 3D8 scFv was co-endocytosed and co-precipitated with representative individual HSPG and CSPG molecules: syndecan-2 (a transmembrane HSPG), glypican-3 (a glycosylphosphatidylinositol (GPI)-anchored HSPG); CD44 (a transmembrane CSPG); and brevican (a GPI-anchored CSPG). Collected data indicate that 3D8 scFv binds to the negatively charged sugar chains of both HSPGs and CSPGs and is then internalized along with these molecules, irrespective of how these proteoglycans are associated with the cell membrane. This is the first study to show that anti-DNA antibodies enter cells via both HSPGs and CSPGs simultaneously. The data may aid understanding of endocytic receptors that bind anti-DNA autoantibodies. The study also provides insight into potential cell membrane targets for macromolecular delivery.
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影响因子：
4.8
作者：
Hansen, James E.;Tse, Chung-Ming;Weisbart, Richard H.
通讯作者：
Weisbart, Richard H.
影响因子：
4.8
作者：
Kim, Young-Rim;Kim, Jeong-Sun;Kim, Yong-Sung
通讯作者：
Kim, Yong-Sung
影响因子：
5.4
作者：
Mondor, I;Ugolini, S;Sattentau, QJ
通讯作者：
Sattentau, QJ
影响因子：
6.9
作者：
Christianson, Helena C.;Belting, Mattias
通讯作者：
Belting, Mattias
影响因子：
4.5
作者：
Fan, Tan-Chi;Chang, Hao-Teng;Chang, Margaret Dah-Tsyr
通讯作者：
Chang, Margaret Dah-Tsyr