title: Approaches to imaging unfolded secretory protein stress in living cells.
abstract: The endoplasmic reticulum (ER) is the point of entry of proteins into the secretory pathway. Nascent peptides interact with the ER quality control machinery that ensures correct folding of the nascent proteins. Failure to properly fold proteins can lead to loss of protein function and cytotoxic aggregation of misfolded proteins that can lead to cell death. To cope with increases in the ER unfolded secretory protein burden, cells have evolved the Unfolded Protein Response (UPR). The UPR is the primary signaling pathway that monitors the state of the ER folding environment. When the unfolded protein burden overwhelms the capacity of the ER quality control machinery, a state termed ER stress, sensor proteins detect accumulation of misfolded peptides and trigger the UPR transcriptional response. The UPR, which is conserved from yeast to mammals, consists of an ensemble of complex signaling pathways that aims at adapting the ER to the new misfolded protein load. To determine how different factors impact the ER folding environment, various tools and assays have been developed. In this review, we discuss recent advances in live cell imaging reporters and model systems that enable researchers to monitor changes in the unfolded secretory protein burden and activation of the UPR and its associated signaling pathways.
authors.affiliation: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lajoie
authors.affiliation: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Elena N
authors.initials: EN
authors.lastname: Fazio
authors.affiliation: Department of Anatomy and Structural Biology, AlbERt Einstein College of Medicine, Forchheimer 640, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Erik L
authors.initials: EL
authors.lastname: Snapp
keywords: BiP; FRAP; Green Fluorescent Protein; IRE1; Kar2; Photobleaching; Quality Control; Transcriptional Reporter; UPRE; yeast