Ligand-receptor complexes formed at the plasma membrane are internalised via various endocytic pathways that influence the ultimate signalling output by regulating the selection of interaction partners by the complex along the trafficking route. We report that, in differentiated cells, activin A-receptor complexes are internalised via clathrin-mediated endocytosis (CME) and macropinocytosis (MP), whereas in human embryonic stem cells (hESCs) internalisation occurs via CME. We further show that hESCs are devoid of MP, which becomes functional upon differentiation towards endothelial cells through mesoderm mediators. Our results reveal, for the first time, that MP is an internalisation route for activin A in differentiated cells, and that MP is not active in hESCs and is induced as cells differentiate.

中文翻译：

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胚胎干细胞缺乏巨胞饮作用，这是分化细胞中激活素 A 的运输途径。

在质膜上形成的配体-受体复合物通过各种内吞途径内化，这​​些途径通过调节复合物沿运输路径选择相互作用伙伴来影响最终的信号输出。我们报告说，在分化细胞中，激活素 A 受体复合物通过网格蛋白介导的内吞作用 (CME) 和巨胞饮作用 (MP) 内化，而在人胚胎干细胞 (hESC) 中，内化通过 CME 发生。我们进一步表明，hESC 缺乏 MP，而 MP 在通过中胚层介质分化为内皮细胞后变得有功能。我们的结果首次揭示，MP 是分化细胞中激活素 A 的内化途径，并且 MP 在 hESC 中不活跃，而是在细胞分化时被诱导。