title: Active JNK-dependent secretion of Drosophila Tyrosyl-tRNA synthetase by loser cells recruits haemocytes during cell competition.
abstract: Cell competition is a process by which the slow dividing cells (losers) are recognized and eliminated from growing tissues. Loser cells are extruded from the epithelium and engulfed by the haemocytes, the Drosophila macrophages. However, how macrophages identify the dying loser cells is unclear. Here we show that apoptotic loser cells secrete Tyrosyl-tRNA synthetase (TyrRS), which is best known as a core component of the translational machinery. Secreted TyrRS is cleaved by matrix metalloproteinases generating MiniTyr and EMAP fragments. EMAP acts as a guiding cue for macrophage migration in the Drosophila larvae, as it attracts the haemocytes to the apoptotic loser cells. JNK signalling and Kish, a component of the secretory pathway, are autonomously required for the active secretion of TyrRS by the loser cells. Altogether, this mechanism guarantees effective removal of unfit cells from the growing tissue.
authors.affiliation: Molecular Oncology Programme, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro, 3, Madrid 28034, Spain.|Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute (CSIC), Avenida Doctor Arce, 37, Madrid 28002, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Casas-Tintó
authors.affiliation: Molecular Oncology Programme, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro, 3, Madrid 28034, Spain.|Vascular Biology and Inflammation Department, Spanish National Cardiovascular Centre (CNIC), Melchor Fernández Almagro, 3, Madrid 28029, Spain.
authors.forename: Fidel-Nicolás
authors.initials: FN
authors.lastname: Lolo
authors.affiliation: Molecular Oncology Programme, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro, 3, Madrid 28034, Spain.|Institute of Cell Biology, University of Bern, Bern CH-3012, Switzerland.|Cell Fitness Lab, Champalimaud Centre for the Unknown, 1400-038 Lisbon, Portugal.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Moreno
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D002633:Chemotaxis; D004330:Drosophila / Q000166:cytology / Q000201:enzymology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006434:Hemocytes / Q000502:physiology*; D006458:Hemolymph / Q000166:cytology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008938:Mitosis; D034622:RNA Interference; D014448:Tyrosine-tRNA Ligase / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C000607996:ksh protein, Drosophila; D048670:MAP Kinase Kinase 4; D014448:Tyrosine-tRNA Ligase