Abstract
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.
Highlights
Multicellular organisms often go through processes to clear unwanted or excess cells
Gulp1 interacts with EphB2 and ephrinB1 during Ephrin receptor (Eph)/ ephrin trogocytosis We previously identified Gulp1 in a proteomic screen as an interactor of clustered EphB2 (Gong et al, 2016)
When U251 responder cells were cocultured with ephrinB1ΔCGFP+ donor HeLa cells, forward trogocytosis was observed (Fig. 1 C), and endogenous Gulp1 was coprecipitated with endogenous EphB2 (Fig. 1 D)
Summary
Multicellular organisms often go through processes to clear unwanted or excess cells. Removal of whole dying cells by phagocytosis is evolutionarily conserved and relatively well described (Flannagan et al, 2012; Freeman and Grinstein, 2014; Arandjelovic and Ravichandran, 2015; Lim et al, 2017). In contrast to the removal of entire cell corpses, there are emerging examples in which cells nibble away parts of neighboring cells in a process termed “trogocytosis,” or cell cannibalism, that is less well understood. Partial eating of host cells by amoebae, a process that contributes to cell killing and tissue invasion, has been proposed to be an ancient form of trogocytosis (Ralston et al, 2014; Ralston, 2015)
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