63 Oral - Cell Division and Cell Growth
Friday April 08, 9:15 AM - 9:30 AM

Authors:
Ke Li ^1,2; Juan Oses-Prieto ²; Alma Burlingame ²; Lily Yeh Jan ^1,2; Yuh Nung Jan ^1,2

Affiliations:
1) Howard Hughes Medical Institute; 2) University of California, San Francisco

Keywords:
s. cell competition; t. cell junctions and adhesion

Cell competition defines an evolutionarily conserved, cell-cell interaction mechanism by which more fit cells (“winners”) eliminate and replace suboptimal cells (“losers”). One classic example is wild-type cells eliminating the adjacent cells bearing mutated or reduced ribosomal protein genes (Rp), emphasizing the significance of the cell-surface interaction between competing populations. Despite recent progress in identifying intracellular molecular events underlying cell competition, little is known regarding how distinct cell populations recognize and compare their relative fitness. Moreover, although mechanical forces have been proposed to regulate cell competition, the components mediating mechanical responses remain elusive. Given the particular interests in the competing interface, we labeled proteins on winner and loser cell surfaces in a spatiotemporal-specific manner and created a quantitative profile using a multiplexed proteomics approach. Using clonal knockdown of Rp in imaginal epithelia, we find ~250 and ~500 proteins are significantly enriched in winner and loser surface proteomes, respectively. Consistent with previous findings, we find autophagy-related proteins are enriched in loser cells, whereas engulfment-related proteins are overrepresented in winner cells. Remarkably, our proteomics data indicates wild-type cells have lower levels of non-muscle myosin expression compared to cells with reduced Rp. Wild-type cells indeed have reduced junctional tension, and restoring junctional tension suppresses cell competition. Interestingly, mechanosensitive channels are highlighted in the winner cells, coincident with their higher calcium signaling. Our results further demonstrate that mechanical stress is required for cell competition, identifying candidate genes mediating mechanical sensing. Efforts are currently underway to perform a proteome-instructed screen to identify novel regulators of cell competition and these results will also be presented.