If you've ever rummaged through the trash to find something you didn't mean to toss out, you can understand one of the problems cells face. Steinberg et al. reveal that a sorting protein prevents cells from throwing away integrins.
Cells continually pluck proteins from the plasma membrane so they can be dispatched to the lysosome for destruction. But some of these proteins are still useful, so the cell diverts them back to the plasma membrane. The nexin SNX17 helps separate the keepers from the trash.
Steinberg et al. devised a new proteomic approach to determine which proteins SNX17 rescues. They reasoned that knocking down SNX17 with RNAi should reduce the abundance of certain proteins because the cell will no longer save these molecules from destruction. Among the 15 proteins whose levels declined after RNAi treatment were the α5 and β1 integrins. Blocking lysosome activity restored the levels of these integrins, confirming that without SNX17’s intervention the proteins end up in the cellular trash.
Because integrins enable cells to get a grip on the extracellular matrix, the researchers tested whether suppressing SNX17 altered cell movement. In tests of crawling speed, cells depleted of SNX17 were swifter than normal. It remains to be seen if the movement of cancer cells—which often swap integrins as they metastasize—is affected by their ability to spare integrins from lysosomal destruction.