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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Banreti AR,Meier P

doi

10.1038/s41467-020-16070-6

subject

Has Abstract

pub_date

2020-05-06 00:00:00

pages

2228

issue

1

issn

2041-1723

pii

10.1038/s41467-020-16070-6

journal_volume

11

pub_type

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