The NMDA receptor regulates competition of epithelial cells in the Drosophila wing.
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Date
2020-05-06ICR Author
Author
Banreti, AR
Meier, P
Type
Journal Article
Metadata
Show full item recordAbstract
Cell competition is an emerging principle that eliminates suboptimal or potentially dangerous cells. For 'unfit' cells to be detected, their competitive status needs to be compared to the collective fitness of cells within a tissue. Here we report that the NMDA receptor controls cell competition of epithelial cells and Myc supercompetitors in the Drosophila wing disc. While clonal depletion of the NMDA receptor subunit NR2 results in their rapid elimination via the TNF/Eiger>JNK signalling pathway, local over-expression of NR2 causes NR2 cells to acquire supercompetitor-like behaviour that enables them to overtake the tissue through clonal expansion that causes, but also relies on, the killing of surrounding cells. Consistently, NR2 is utilised by Myc clones to provide them with supercompetitor status. Mechanistically, we find that the JNK>PDK signalling axis in 'loser' cells reprograms their metabolism, driving them to produce and transfer lactate to winners. Preventing lactate transfer from losers to winners abrogates NMDAR-mediated cell competition. Our findings demonstrate a functional repurposing of NMDAR in the surveillance of tissue fitness.
Collections
Subject
Mitochondria
Epithelial Cells
Animals
Drosophila
Lactic Acid
Tumor Necrosis Factor-alpha
DNA-Binding Proteins
Drosophila Proteins
Receptors, N-Methyl-D-Aspartate
Transcription Factors
Signal Transduction
Apoptosis
MAP Kinase Signaling System
Wings, Animal
Research team
Cell Death and Immunity
Language
eng
Date accepted
2020-04-08
License start date
2020-05-06
Citation
Nature communications, 2020, 11 (1), pp. 2228 - ?
Publisher
NATURE PUBLISHING GROUP