TITLE

Endoplasmic Reticulum Membrane Reorganization Is Regulated by Ionic Homeostasis

AUTHOR(S)
Varadarajan, Shankar; Tanaka, Kayoko; Smalley, Joshua L.; Bampton, Edward T. W.; Pellecchia, Maurizio; Dinsdale, David; Willars, Gary B.; Cohen, Gerald M.
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Recently we described a new, evolutionarily conserved cellular stress response characterized by a reversible reorganization of endoplasmic reticulum (ER) membranes that is distinct from canonical ER stress and the unfolded protein response (UPR). Apogossypol, a putative broad spectrum BCL-2 family antagonist, was the prototype compound used to induce this ER membrane reorganization. Following microarray analysis of cells treated with apogossypol, we used connectivity mapping to identify a wide range of structurally diverse chemicals from different pharmacological classes and established their ability to induce ER membrane reorganization. Such structural diversity suggests that the mechanisms initiating ER membrane reorganization are also diverse and a major objective of the present study was to identify potentially common features of these mechanisms. In order to explore this, we used hierarchical clustering of transcription profiles for a number of chemicals that induce membrane reorganization and discovered two distinct clusters. One cluster contained chemicals with known effects on Ca2+ homeostasis. Support for this was provided by the findings that ER membrane reorganization was induced by agents that either deplete ER Ca2+ (thapsigargin) or cause an alteration in cellular Ca2+ handling (calmodulin antagonists). Furthermore, overexpression of the ER luminal Ca2+ sensor, STIM1, also evoked ER membrane reorganization. Although perturbation of Ca2+ homeostasis was clearly one mechanism by which some agents induced ER membrane reorganization, influx of extracellular Na+ but not Ca2+ was required for ER membrane reorganization induced by apogossypol and the related BCL-2 family antagonist, TW37, in both human and yeast cells. Not only is this novel, non-canonical ER stress response evolutionary conserved but so also are aspects of the mechanism of formation of ER membrane aggregates. Thus perturbation of ionic homeostasis is important in the regulation of ER membrane reorganization.
ACCESSION #
87624761

 

Related Articles

  • Intracellular trafficking and secretion of mouse mesencephalic astrocyte-derived neurotrophic factor. Oh-hashi, Kentaro; Tanaka, Kensuke; Koga, Hisashi; Hirata, Yoko; Kiuchi, Kazutoshi // Molecular & Cellular Biochemistry;Apr2012, Vol. 363 Issue 1/2, p35 

    Recently, mesencephalic astrocyte-derived neurotrophic factor (MANF) has been reported to prevent cell death under some pathophysiological conditions. MANF, also referred to as arginine rich, mutated in early stage of tumors (Armet), was identified as an endoplasmic reticulum (ER)...

  • Phenyl Acyl Acids Attenuate the Unfolded Protein Response in Tunicamycin-Treated Neuroblastoma Cells. Zamarbide, Marta; Martinez-Pinilla, Eva; Ricobaraza, Ana; Aragón, Tomás; Franco, Rafael; Pérez-Mediavilla, Alberto // PLoS ONE;Aug2013, Vol. 8 Issue 8, p1 

    Understanding how neural cells handle proteostasis stress in the endoplasmic reticulum (ER) is important to decipher the mechanisms that underlie the cell death associated with neurodegenerative diseases and to design appropriate therapeutic tools. Here we have compared the sensitivity of a...

  • TRAPPC9 Mediates the Interaction between p150Glued and COPII Vesicles at the Target Membrane. Min Zong; Ayano Satoh; Mei Kuen Yu; Ka Yu Siu; Wing Yan Ng; Hsiao Chang Chan; Tanner, Julian A.; Sidney Yu // PLoS ONE;Jan2012, Vol. 7 Issue 1, p1 

    Background: The transport of endoplasmic reticulum (ER)-derived COPII vesicles toward the ER-Golgi intermediate compartment (ERGIC) requires cytoplasmic dynein and is dependent on microtubules. p150Glued, a subunit of dynactin, has been implicated in the transport of COPII vesicles via its...

  • Roles of Molecular Chaperones in Endoplasmic Reticulum (ER) Quality Control and ER-Associated Degradation (ERAD). Nishikawa, Shuh-ichi; Brodsky, Jeffrey L.; Nakatsukasa, Kunio // Journal of Biochemistry;May2005, Vol. 137 Issue 5, p551 

    Secreted proteins are synthesized at the endoplasmic reticulum (ER), and a quality control mechanism in the ER is essential to maintain secretory pathway homeostasis. Newly synthesized soluble and integral membrane secreted proteins fold into their native conformations with the aid of ER...

  • DAP-kinase is a mediator of endoplasmic reticulum stress-induced caspase activation and autophagic cell death. Gozuacik, D; Bialik, S; Raveh, T; Mitou, G; Shohat, G; Sabanay, H; Mizushima, N; Yoshimori, T; Kimchi, A // Cell Death & Differentiation;Dec2008, Vol. 15 Issue 12, p1875 

    Damage to endoplasmic reticulum (ER) homeostasis that cannot be corrected by the unfolded protein response activates cell death. Here, we identified death-associated protein kinase (DAPk) as an important component in the ER stress-induced cell death pathway. DAPk−/− mice are...

  • Coupling endoplasmic reticulum stress to the cell-death program: a novel HSP90-independent role for the small chaperone protein p23. Rao, R. V.; Niazi, K.; Mollahan, P.; Mao, X.; Crippen, D.; Poksay, K. S.; Chen, S.; Bredesen, D. E. // Cell Death & Differentiation;Mar2006, Vol. 13 Issue 3, p415 

    The endoplasmic reticulum (ER) is the principal organelle for the biosynthesis of proteins, steroids and many lipids, and is highly sensitive to alterations in its environment. Perturbation of Ca2+ homeostasis, elevated secretory protein synthesis, deprivation of glucose or other sugars, altered...

  • Cadmium induces neuronal cell death through reactive oxygen species activated by GADD153. Seungwoo Kim; Hyo-Soon Cheon; So-Young Kim; Yong-Sung Juhnn; Young-Youl Kim // BMC Cell Biology;2013, Vol. 14 Issue 1, p1 

    Background: Cadmium(Cd), a heavy metal, which has a potent harmful effects, is a highly stress-inducible material that is robustly expressed following disruption of homeostasis in the endoplasmic reticulum (ER) (so-called ER stress). The mechanism Cd induced cell death of neuroblastoma cells...

  • Calnexin-dependent regulation of tunicamycin-induced apoptosis in breast carcinoma MCF-7 cells. Delom, F.; Emadali, A.; Cocolakis, E.; Lebrun, J.-J.; Nantel, A.; Chevet, E. // Cell Death & Differentiation;Mar2007, Vol. 14 Issue 3, p586 

    The endoplasmic reticulum (ER) has evolved specific mechanisms to ensure protein folding as well as the maintenance of its own homeostasis. When these functions are not achieved, specific ER stress signals are triggered to activate either adaptive or apoptotic responses. Here, we demonstrate...

  • GRP94 reduces cell death in SH-SY5Y cells perturbated calcium homeostasis. Bando, Y.; Katayama, T.; Aleshin, A. N.; Manabe, T.; Tohyama, M. // Apoptosis;Jul2004, Vol. 9 Issue 4, p501 

    The endoplasmic reticulum (ER) resident—94 kDa glucose-regulated protein (GRP94), plays a pivotal role in cell death due to ER stress. In our study expression of GRP94 was increased in human neuroblastoma SH-SY5Y cells due to exposure to calcium ionophore A23187. A23187-mediated cell...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics