Tension testing in adherent cells
L ike soloing rock climbers, adherent cells need a good handhold to survive. Ma et al. now identify an adaptor protein that monitors the cell's grip and signals death if the grip fails. Death following detachment, known as anoikis, is a form of programmed cell death that ensures the disposal of displaced adherent cells. Lack of anoikis is thought to give cells metastatic potential. A number of survival factors have been identifi ed that are activated by integrin attachment to the extracellular matrix. Binding to soluble matrix fragments, rather than to a fi xed matrix, does not prevent anoikis. This difference suggests that mechanical tension is also being measured. Inside the cell, integrins associate with signaling adaptor proteins of the Shc family. One family member, p66 Shc , has been suggested to promote apoptosis. The team now shows that an epithelial cell line that resists anoikis does not express p66 Shc. Giving these cells back some p66 Shc reestablished detachment-induced death. Normal epithelial and endothelial cells express p66 Shc. Thus, p66 Shc must only trigger death upon cell detachment. p66 Shc did not induce anoikis by the same mechanism as it induces apoptosis. For apoptosis, p66 Shc enters mitochondria. But for anoikis, p66 Shc associated with integrins and activated the actin cytokeleton regulator RhoA. RhoA increases tension between cell attachment points by inducing stress fi ber formation. Inhibiting contraction of these fi bers, the team showed, curbed anoikis. The authors therefore suggest that the cell continuously checks its tension by contracting its stress fi bers—like checking from the inside of a tent whether the pegs are secure. If the cell contracts easily, then p66 Shc signals that external anchors are missing and that, for this cell, the camping trip is over. I n times of stress, cells reduce translation to conserve resources. Hoyle et al. now report that many of the backed-up untranslated mRNAs hang out in a new type of cytoplasmic granule called EGP bodies. The stress of glucose starvation in yeast abruptly slows translation. So Hoyle et al. wondered what happens to the stalled translation machinery. They discovered that three translation factors, eIF4E, eIF4G, and Pab1p (E, G, and P), huddled together into four or fi ve cytoplasmic foci. The binding of E, G, and P to untranslated mRNAs was thought to commit the transcripts to translation. But when the translation factors formed quiescent foci, the mRNAs went …