Article ; Online: The NMDA receptor regulates competition of epithelial cells in the Drosophila wing.
2020 Volume 11, Issue 1, Page(s) 2228
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 ... ...
| 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. |
|---|---|
| MeSH term(s) | Animals ; Apoptosis/genetics ; DNA-Binding Proteins/metabolism ; Drosophila/genetics ; Drosophila/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Epithelial Cells/metabolism ; Lactic Acid/metabolism ; MAP Kinase Signaling System/genetics ; Mitochondria/metabolism ; Receptors, N-Methyl-D-Aspartate/genetics ; Receptors, N-Methyl-D-Aspartate/metabolism ; Signal Transduction/genetics ; Transcription Factors/metabolism ; Tumor Necrosis Factor-alpha/genetics ; Tumor Necrosis Factor-alpha/metabolism ; Wings, Animal/growth & development ; Wings, Animal/metabolism |
| Chemical Substances | DNA-Binding Proteins ; Drosophila Proteins ; Myc protein, Drosophila ; Nmdar1 protein, Drosophila ; Receptors, N-Methyl-D-Aspartate ; Transcription Factors ; Tumor Necrosis Factor-alpha ; Lactic Acid (33X04XA5AT) |
| Language | English |
| Publishing date | 2020-05-06 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2553671-0 |
| ISSN | 2041-1723 ; 2041-1723 |
| ISSN (online) | 2041-1723 |
| ISSN | 2041-1723 |
| DOI | 10.1038/s41467-020-16070-6 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.