ABU to perform under stress

report on page 639 identifies a family of proteins that are important when worms are unable to deal with ER stress. The results from Urano et al. suggest that these proteins are receptors for incorrectly folded proteins at the ER. In worms and other eukaryotes, conditions that stress the ER, such as those that inhibit glycosylation, activate the unfolded protein response (UPR). The UPR comprises several signaling pathways that increase the protein folding capacity of the ER through the induction of chaperones and other protein processing and trafficking components. The UPR does not, however, explain everything. Using microarrays, Urano et al. identified a default pathway activated in worms under ER stress A when the UPR is blocked. Among the genes identified were nine members of a family they named abu , for activated in blocked UPR. RNAi inhibition of one or more ABU proteins in UPR-deficient mutants severely impaired their survival during Selectin flexible cells eukocytes use glycoprotein ligands to grab onto selectins on blood vessel walls and roll along with the blood flow. The longer the cell can roll without detaching, the greater its chances are of responding to chemoattractants telling it to traverse the endothelium at a site of inflammation. Now, on page 787, Yago et al. show that flexibility helps a cell avoid detachment when circulatory forces are high. As shear force increases with higher blood pressure and smaller vessel size, leukocytes can maintain a stable rolling velocity, an ability known as an automatic braking system (ABS). Artificial microspheres containing certain ligands also roll on selectins, but lack an ABS—under high forces, their rolling velocity increases, and they are more apt to L ER stress. In wild-type worms, interference with ABU function by RNAi induced ER stress genes, indicating that the ABU proteins may also function under nonstress conditions. Localization experiments indicated that ABU-1 is an ER-localized integral membrane protein. The ABU family resembles mammalian scavenger receptors, plasma membrane proteins that bind extracellular proteins that are oxidized or otherwise chemically modified. ABU proteins may serve a similar function at the ER, although a direct interaction with improperly folded proteins has yet to be shown. Mammals do not have obvious orthologues of ABU proteins. But recent results showing that the ER and plasma membrane may fuse during ER stress induces abu-1 (white) when UPR pathways are blocked (bottom). phagocytosis suggest that the distinction between plasma membrane proteins and …