Renal cells activate the platelet receptor CLEC-2 through podoplanin.
Renal cells activate the platelet receptor CLEC-2 through podoplanin.
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DOI：
10.1042/bj20071216
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发表时间：
2008-04-01
期刊：
影响因子：
--
通讯作者：
O'Callaghan CA
中科院分区：
文献类型：
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作者：
Christou CM;Pearce AC;Watson AA;Mistry AR;Pollitt AY;Fenton-May AE;Johnson LA;Jackson DG;Watson SP;O'Callaghan CA
我们最近发现C型凝集素样受体CLEC-2在血小板上表达，并通过蛇毒毒素红细胞素介导强大的血小板聚集。此外，我们还提供了间接的证据，CLEC-2的内源性配体在肾细胞表达人类免疫缺陷病毒1型（HIV-1）。这种推定的配体通过其掺入病毒包膜并结合血小板上的CLEC-2来促进HIV的传播。本研究的目的是鉴定这些细胞上与血小板上的CLEC-2结合的配体。重组CLEC-2表现出对HIV可以生长的293 T细胞的特异性结合。此外，293 T细胞激活血小板和CLEC-2转染的DT-40 B细胞。跨膜蛋白podoplanin在293 T细胞上被鉴定，并被证明介导293 T细胞与CLEC-2的结合和CLEC-2转染的DT-40 B细胞的293 T细胞活化。Podoplanin在肾细胞（足细胞）上表达。此外，CLEC-2和podoplanin之间的直接相互作用被证实使用表面等离子体共振，并被证明是独立的CLEC-2的糖基化。相互作用的亲和力为24.5 ± 3.7μM。本研究确定podoplanin作为肾细胞上CLEC-2的配体。
We have recently shown that the C-type lectin-like receptor, CLEC-2, is expressed on platelets and that it mediates powerful platelet aggregation by the snake venom toxin, rhodocytin. In addition, we have provided indirect evidence for an endogenous ligand for CLEC-2 in renal cells expressing human immunodeficiency virus type 1 (HIV-1). This putative ligand facilitates transmission of HIV through its incorporation into the viral envelope and binding to CLEC-2 on platelets. The aim of this study was to identify the ligand on these cells which binds to CLEC-2 on platelets. Recombinant CLEC-2 exhibits specific binding to 293T cells in which the HIV can be grown. Further, 293T cells activate both platelets and CLEC-2-transfected DT-40 B cells. The transmembrane protein podoplanin was identified on 293T cells and demonstrated to mediate both binding of 293T cells to CLEC-2 and 293T cell activation of CLEC-2-transfected DT-40 B cells. Podoplanin is expressed on renal cells (podocytes). Further, a direct interaction between CLEC-2 and podoplanin was confirmed using surface plasmon resonance and was shown to be independent of glycosylation of CLEC-2. The interaction has an affinity of 24.5 ± 3.7μM. The present study identifies podoplanin as a ligand for CLEC-2 on renal cells.