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The NMDA receptor regulates competition of epithelial cells in the Drosophila wing.

Nature communications (2020-05-08)
Agnes R Banreti, Pascal Meier
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Roche
Anti-GFP, from mouse IgG1κ (clones 7.1 and 13.1)
Sigma-Aldrich
Sodium L-lactate, ≥99.0% (NT)
Sigma-Aldrich
M16 Medium, With sodium bicarbonate and lactic acid, without penicillin and streptomycin, liquid, sterile-filtered
Sigma-Aldrich
D(−)-2-Amino-5-phosphonopentanoic acid, NMDA receptor antagonist
Sigma-Aldrich
Ifenprodil (+)-tartrate salt
Sigma-Aldrich
PEAQX tetrasodium hydrate, ≥98% (HPLC)