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The NMDA receptor regulates competition of epithelial cells in the Drosophila wing
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The NMDA receptor regulates competition of epithelial cells in the Drosophila wing
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Journal Article
The NMDA receptor regulates competition of epithelial cells in the Drosophila wing
2020
Overview
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.
Cell competition among epithelial cells allows removal of unfit or dangerous cells. Here, the authors show that the NMDA receptor is an important determinant of cell fitness in the
Drosophila
wing, also in the context of Myc super-competitor cells, with “loser” cells contributing metabolitic fuel to “winner” cells.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/2
/ 13/95
/ 64
/ 64/24
/ 96
/ Animals
/ DNA-Binding Proteins - metabolism
/ Drosophila Proteins - genetics
/ Drosophila Proteins - metabolism
/ Epithelial Cells - metabolism
/ Fitness
/ Glutamic acid receptors (ionotropic)
/ Humanities and Social Sciences
/ Insects
/ MAP Kinase Signaling System - genetics
/ N-Methyl-D-aspartic acid receptors
/ Receptors, N-Methyl-D-Aspartate - genetics
/ Receptors, N-Methyl-D-Aspartate - metabolism
/ Science
/ Signal Transduction - genetics
/ Transcription Factors - metabolism
/ Tumor Necrosis Factor-alpha - genetics
/ Tumor Necrosis Factor-alpha - metabolism
