Please use this identifier to cite or link to this item:
Title: A novel cellular stress response characterised by a rapid reorganisation of membranes of the endoplasmic reticulum.
Authors: Varadarajan, S
Bampton, ET
Smalley, JL
Tanaka, K
Caves, RE
Butterworth, M
Wei, J
Pellecchia, M
Mitcheson, J
Gant, TW
Dinsdale, D
Cohen, GM
First Published: 7-Sep-2012
Citation: CELL DEATH DIFFER, 2012
Abstract: Canonical endoplasmic reticulum (ER) stress, which occurs in many physiological and disease processes, results in activation of the unfolded protein response (UPR). We now describe a new, evolutionarily conserved cellular stress response characterised by a striking, but reversible, reorganisation of ER membranes that occurs independently of the UPR, resulting in impaired ER transport and function. This reorganisation is characterised by a dramatic redistribution and clustering of ER membrane proteins. ER membrane aggregation is regulated, in part, by anti-apoptotic BCL-2 family members, particularly MCL-1. Using connectivity mapping, we report the widespread occurrence of this stress response by identifying several structurally diverse chemicals from different pharmacological classes, including antihistamines, antimalarials and antipsychotics, which induce ER membrane reorganisation. Furthermore, we demonstrate the potential of ER membrane aggregation to result in pathological consequences, such as the long-QT syndrome, a cardiac arrhythmic abnormality, arising because of a novel trafficking defect of the human ether-a-go-go-related channel protein from the ER to the plasma membrane. Thus, ER membrane reorganisation is a feature of a new cellular stress pathway, clearly distinct from the UPR, with important consequences affecting the normal functioning of the ER.Cell Death and Differentiation advance online publication, 7 September 2012; doi:10.1038/cdd.2012.108.
DOI Link: 10.1038/cdd.2012.108
eISSN: 1476-5403
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Biochemistry

Files in This Item:
There are no files associated with this item.

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.