Gulp1 controls Eph/ephrin trogocytosis and is important for cell rearrangements during development

J Cell Biol. 2019 Oct 7;218(10):3455-3471. doi: 10.1083/jcb.201901032. Epub 2019 Aug 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cells, Cultured
  • Ephrins / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Receptors, Eph Family / metabolism*
  • Signal Transduction

Substances

  • Adaptor Proteins, Signal Transducing
  • Ephrins
  • GULP1 protein, human
  • Receptors, Eph Family