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Hyperactive Rac converts sublethal to lethal trogocytosis in vivo - PubMed

5 hours ago
  • #RacG12V
  • #trogocytosis
  • #cell-engulfment
  • Hyperactive RacG12V causes border cells in Drosophila ovary to switch from sublethal to lethal trogocytosis, leading to cannibalization of nurse cells.
  • Rac-enhanced chimeric-antigen-receptor macrophages (RaceCAR-Ms) were engineered to mimic this mechanism for killing cancer cells through avid engulfment.
  • Larger bites taken by hyperactive RacG12V-expressing border cells trigger rapid shrinkage, nuclear damage, caspase activation, and germline death, which spreads through the nurse cell syncytium.
  • Both sublethal and lethal trogocytosis depend on Rac and the engulfment receptor Draper, with increased Draper expression or JNK activity also causing germline death independently of Rac.
  • Clonal analysis shows that small groups of follicle cells with RacG12V induce caspase in neighbors, while larger clones are needed for germline killing, revealing how few hyperactive cells can destroy a larger mass.