Max Planck Institute of Neurobiology, Department of Molecules-Signaling-Development, Munich-Martinsried, Germany.
Department of Cell and Systems Biology, University of Toronto, Toronto, Canada.
J Cell Biol. 2019 Oct 7;218(10):3455-3471. doi: 10.1083/jcb.201901032. Epub 2019 Aug 13.
Trogocytosis, in which cells nibble away parts of neighboring cells, is an intercellular cannibalism process conserved from protozoa to mammals. Its underlying molecular mechanisms are not well understood and are likely distinct from phagocytosis, a process that clears entire cells. Bi-directional contact repulsion induced by Eph/ephrin signaling involves transfer of membrane patches and full-length Eph/ephrin protein complexes between opposing cells, resembling trogocytosis. Here, we show that the phagocytic adaptor protein Gulp1 regulates EphB/ephrinB trogocytosis to achieve efficient cell rearrangements of cultured cells and during embryonic development. Gulp1 mediates trogocytosis bi-directionally by dynamic engagement with EphB/ephrinB protein clusters in cooperation with the Rac-specific guanine nucleotide exchange factor Tiam2. Ultimately, Gulp1's presence at the Eph/ephrin cluster is a prerequisite for recruiting the endocytic GTPase dynamin. These results suggest that EphB/ephrinB trogocytosis, unlike other trogocytosis events, uses a phagocytosis-like mechanism to achieve efficient membrane scission and engulfment.
细胞胞饮作用，即细胞吞噬邻近细胞的部分内容，是一种从原生动物到哺乳动物中保守的细胞间噬食过程。其潜在的分子机制尚未得到很好的理解，可能与吞噬作用不同，后者可以清除整个细胞。Eph/ephrin 信号诱导的双向接触排斥涉及到膜斑和全长 Eph/ephrin 蛋白复合物在相对细胞之间的转移，类似于细胞胞饮作用。在这里，我们表明吞噬作用衔接蛋白 Gulp1 调节 EphB/ephrinB 细胞胞饮作用，以实现培养细胞和胚胎发育过程中的有效细胞重排。Gulp1 通过与 Rac 特异性鸟嘌呤核苷酸交换因子 Tiam2 合作，动态参与 EphB/ephrinB 蛋白簇，双向介导细胞胞饮作用。最终，Gulp1 在 Eph/ephrin 簇的存在是招募内吞 GTP 酶 dynamin 的前提条件。这些结果表明，与其他细胞胞饮作用事件不同，EphB/ephrinB 细胞胞饮作用使用类似吞噬作用的机制来实现有效的膜分裂和吞噬作用。
