UCD Conway Institute, Conway SPHERE Research Group, School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.
UCD Institute for Discovery, O'Brien Centre for Science, University College Dublin, Dublin, Ireland.
Proteomics. 2018 May;18(9):e1700419. doi: 10.1002/pmic.201700419.
It was previously demonstrated that the WNT/β-catenin pathway is present and active in platelets and established that the canonical WNT ligand, WNT-3a, suppresses platelet adhesion and activation. In nucleated cells, β-catenin, the key downstream effector of this pathway, is a dual function protein, regulating the coordination of gene transcription and cell-cell adhesion. The specific role of β-catenin in the anucleate platelet however remains elusive. Here, a label-free quantitative proteomic analysis of β-catenin immunoprecipitates from human platelets is performed and nine co-immunoprecipitating proteins are identified. Three of the co-immunoprecipitating proteins (α-catenin-1, cadherin-6, and β-catenin-interacting protein 1) are common to both resting and activated conditions. Bioinformatics analysis of proteomics data reveal a strong association of the dataset with both cadherin adherens junctions and regulators of WNT signaling. It is then verified that platelet β-catenin and cadherin-6 interact and that this interaction is regulated by the activation state of the platelet. Taken together, this proteomics study suggests a novel role for β-catenin in human platelets where it interacts with platelet cadherins and associated junctional proteins.
先前的研究表明，WNT/β-连环蛋白通路存在于血小板中且具有活性，并证实经典的 WNT 配体 WNT-3a 可抑制血小板黏附和激活。在有核细胞中，β-连环蛋白是该通路的关键下游效应物，是一种具有双重功能的蛋白质，可调节基因转录和细胞间黏附的协调。然而，β-连环蛋白在无核血小板中的具体作用仍不清楚。在此，对来自人血小板的β-连环蛋白免疫沉淀物进行了无标记定量蛋白质组学分析，鉴定出 9 种共免疫沉淀蛋白。其中 3 种共免疫沉淀蛋白（α-连环蛋白-1、钙黏蛋白-6 和 β-连环蛋白相互作用蛋白 1）在静息和激活状态下均存在。蛋白质组学数据的生物信息学分析表明，数据集与钙黏蛋白黏着连接以及 WNT 信号转导调节剂有很强的关联。然后验证了血小板β-连环蛋白与钙黏蛋白-6 相互作用，且这种相互作用受血小板激活状态的调节。综上所述，这项蛋白质组学研究表明，β-连环蛋白在人血小板中具有新的作用，其与血小板钙黏蛋白和相关连接蛋白相互作用。
