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 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 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 phagocytosis suggest that the distinction between plasma membrane proteins and ER proteins may not be as clear as previously suggested. Thus, the scavenger receptors may be able to fill in for ABU proteins in the ER. ▪