期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 289, 期 52, 页码 35695-35710出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.584284
关键词
-
资金
- Wellcome Trust [088410/Z/09/Z, 100262/Z/12/Z]
- NIH [R37AI43542]
- MRC
- Medical Research Council
- Advantage West Midlands
- Wellcome Trust [100262/Z/12/Z, 088410/Z/09/Z] Funding Source: Wellcome Trust
- Medical Research Council [G1100134, MC_UU_12010/2, MC_U137884182] Funding Source: researchfish
- MRC [G1100134, MC_UU_12010/2, MC_U137884182] Funding Source: UKRI
The interaction of C-type lectin receptor 2 (CLEC-2) on platelets with Podoplanin on lymphatic endothelial cells initiates platelet signaling events that are necessary for prevention of blood-lymph mixing during development. In the present study, we show that CLEC-2 signaling via Src family and Syk tyrosine kinases promotes platelet adhesion to primary mouse lymphatic endothelial cells at low shear. Using supported lipid bilayers containing mobile Podoplanin, we further show that activation of Src and Syk in platelets promotes clustering of CLEC-2 and Podoplanin. Clusters of CLEC-2-bound Podoplanin migrate rapidly to the center of the platelet to form a single structure. Fluorescence lifetime imaging demonstrates that molecules within these clusters are within 10 nm of one another and that the clusters are disrupted by inhibition of Src and Syk family kinases. CLEC-2 clusters are also seen in platelets adhered to immobilized Podoplanin using direct stochastic optical reconstruction microscopy. These findings provide mechanistic insight by which CLEC-2 signaling promotes adhesion to Podoplanin and regulation of Podoplanin signaling, thereby contributing to lymphatic vasculature development.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据