Highly glycosylated MUC1 mediates high affinity L-selectin binding at the human endometrial surface.
Highly glycosylated MUC1 mediates high affinity L-selectin binding at the human endometrial surface.
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DOI：
10.1186/s12951-021-00793-9
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发表时间：
2021-02-17
影响因子：
10.2
通讯作者：
Conlan RS
中科院分区：
文献类型：
--
作者：
Francis LW;Yao SN;Powell LC;Griffiths S;Berquand A;Piasecki T;Howe W;Gazze AS;Farach-Carson MC;Constantinou P;Carson D;Margarit L;Gonzalez D;Conlan RS
跨膜O-糖基化粘蛋白和胚胎之间的唾液酸化-路易斯X/L-选择素高亲和力结合相互作用已经涉及人类生殖系统内的植入过程。然而，这些粘蛋白在子宫内膜细胞表面的粘附特性是难以解决的，由于已知的体内模型和人类生殖系统之间的差异和缺乏敏感性，在目前的体外模型。为了克服这些局限性，在体外模型的人子宫内膜上皮询问与单分子力光谱（SMFS）描绘的分子构型的粘蛋白介导的高亲和力L-选择素结合所需的人胚胎植入。这项研究表明，MUC 1有助于HEC-1细胞表面的内在和外在粘附特性。MUC 1在细胞表面上的高表达导致显著增加的内在粘附力（148 pN对271 pN，p < 0.001），而在siRNA介导的MUC 1消融后，该粘附力显著降低（271 pN对118 pN，p < 0.001）。虽然显示糖基化升高的MUC 1的高表达导致细胞表面的强外源性（> 400 pN）L-选择素结合，但糖基化降低的MUC 1的低表达导致显著更少（≤200 pN）的结合事件。MUC 1的最佳水平以及蛋白质的高度糖基化修饰对于高亲和力L-选择素结合是至关重要的。这项研究表明，MUC 1有助于细胞粘附特性，这可能有助于促进滋养层细胞结合子宫内膜细胞表面通过L-选择素/唾液酸-路易斯X粘附系统植入后。
Sialyl-Lewis X/L-selectin high affinity binding interactions between transmembrane O-glycosylated mucins proteins and the embryo have been implicated in implantation processes within the human reproductive system. However, the adhesive properties of these mucins at the endometrial cell surface are difficult to resolve due to known discrepancies between in vivo models and the human reproductive system and a lack of sensitivity in current in vitro models. To overcome these limitations, an in vitro model of the human endometrial epithelial was interrogated with single molecule force spectroscopy (SMFS) to delineate the molecular configurations of mucin proteins that mediate the high affinity L-selectin binding required for human embryo implantation. This study reveals that MUC1 contributes to both the intrinsic and extrinsic adhesive properties of the HEC-1 cellular surface. High expression of MUC1 on the cell surface led to a significantly increased intrinsic adhesion force (148 pN vs. 271 pN, p < 0.001), whereas this adhesion force was significantly reduced (271 pN vs. 118 pN, p < 0.001) following siRNA mediated MUC1 ablation. Whilst high expression of MUC1 displaying elevated glycosylation led to strong extrinsic (> 400 pN) L-selectin binding at the cell surface, low expression of MUC1 with reduced glycosylation resulted in significantly less (≤200 pN) binding events. An optimal level of MUC1 together with highly glycosylated decoration of the protein is critical for high affinity L-selectin binding. This study demonstrates that MUC1 contributes to cellular adhesive properties which may function to facilitate trophoblast binding to the endometrial cell surface through the L-selectin/sialyl-Lewis x adhesion system subsequent to implantation.
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影响因子：
3.1
作者：
Laniewski, Pawel;Gomez, Adriana;Herbst-Kralovetz, Melissa M.
通讯作者：
Herbst-Kralovetz, Melissa M.
影响因子：
3.7
作者：
Gipson IK;Spurr-Michaud S;Tisdale A;Menon BB
通讯作者：
Menon BB
影响因子：
11.2
作者：
Hsu YT;Osmulski P;Wang Y;Huang YW;Liu L;Ruan J;Jin VX;Kirma NB;Gaczynska ME;Huang TH
通讯作者：
Huang TH
影响因子：
6.1
作者：
Dharmaraj, N.;Chapela, P. J.;Carson, D. D.
通讯作者：
Carson, D. D.
影响因子：
4.8
作者：
Gaemers, IC;Vos, HL;Hilkens, J
通讯作者：
Hilkens, J