Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Luminal Ca2+ depletion during the unfolded protein response in Xenopus oocytes: cause and consequence.
Paredes RM
,
Bollo M
,
Holstein D
,
Lechleiter JD
.
???displayArticle.abstract???
The endoplasmic reticulum (ER) is a Ca(2+) storing organelle that plays a critical role in the synthesis, folding and post-translational modifications of many proteins. The ER enters into a condition of stress when the load of newly synthesized proteins exceeds its folding and processing capacity. This activates a signal transduction pathway called the unfolded protein response (UPR) that attempts to restore homeostasis. The precise role of ER Ca(2+) in the initiation of the UPR has not been defined. Specifically, it has not been established whether ER Ca(2+) dysregulation is a cause or consequence of ER stress. Here, we report that partial depletion of ER Ca(2+) stores induces a significant induction of the UPR, and leads to the retention of a normally secreted protein Carboxypeptidase Y. Moreover, inhibition of protein glycosylation by tunicamycin rapidly induced an ER Ca(2+) leak into the cytosol. However, blockade of the translocon with emetine inhibited the tunicamycin-induced Ca(2+) release. Furthermore, emetine treatment blocked elF2α phosphorylation and reduced expression of the chaperone BiP. These findings suggest that Ca(2+) may be both a cause and a consequence of ER protein misfolding. Thus, it appears that ER Ca(2+) leak is a significant co-factor for the initiation of the UPR.
Arduíno,
Endoplasmic reticulum and mitochondria interplay mediates apoptotic cell death: relevance to Parkinson's disease.
2009, Pubmed
Arduíno,
Endoplasmic reticulum and mitochondria interplay mediates apoptotic cell death: relevance to Parkinson's disease.
2009,
Pubmed
Benali-Furet,
Hepatitis C virus core triggers apoptosis in liver cells by inducing ER stress and ER calcium depletion.
2005,
Pubmed
Berridge,
The endoplasmic reticulum: a multifunctional signaling organelle.
2002,
Pubmed
Bertolotti,
Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response.
2000,
Pubmed
Bollo,
Calcineurin interacts with PERK and dephosphorylates calnexin to relieve ER stress in mammals and frogs.
2010,
Pubmed
,
Xenbase
Buchberger,
Protein quality control in the cytosol and the endoplasmic reticulum: brothers in arms.
2010,
Pubmed
Burdakov,
Intraluminal calcium as a primary regulator of endoplasmic reticulum function.
2005,
Pubmed
Camacho,
Calreticulin inhibits repetitive intracellular Ca2+ waves.
1995,
Pubmed
,
Xenbase
Carlberg,
Short exposures to tunicamycin induce apoptosis in SV40-transformed but not in normal human fibroblasts.
1996,
Pubmed
Chami,
Role of SERCA1 truncated isoform in the proapoptotic calcium transfer from ER to mitochondria during ER stress.
2008,
Pubmed
Cheung,
Mechanism of Ca2+ disruption in Alzheimer's disease by presenilin regulation of InsP3 receptor channel gating.
2008,
Pubmed
Cnop,
Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities.
2005,
Pubmed
Cox,
Measuring signaling by the unfolded protein response.
2011,
Pubmed
Crowley,
Secretory proteins move through the endoplasmic reticulum membrane via an aqueous, gated pore.
1994,
Pubmed
Deniaud,
Endoplasmic reticulum stress induces calcium-dependent permeability transition, mitochondrial outer membrane permeabilization and apoptosis.
2008,
Pubmed
Erdmann,
Interaction of calmodulin with Sec61α limits Ca2+ leakage from the endoplasmic reticulum.
2011,
Pubmed
Falcke,
Modeling the dependence of the period of intracellular Ca2+ waves on SERCA expression.
2003,
Pubmed
,
Xenbase
Finger,
Analysis of two mutated vacuolar proteins reveals a degradation pathway in the endoplasmic reticulum or a related compartment of yeast.
1993,
Pubmed
Flourakis,
Passive calcium leak via translocon is a first step for iPLA2-pathway regulated store operated channels activation.
2006,
Pubmed
Giunti,
Both translocon and a cation channel are involved in the passive Ca2+ leak from the endoplasmic reticulum: a mechanistic study on rat liver microsomes.
2007,
Pubmed
Hamman,
BiP maintains the permeability barrier of the ER membrane by sealing the lumenal end of the translocon pore before and early in translocation.
1998,
Pubmed
Hammond,
Quality control in the secretory pathway.
1995,
Pubmed
Hanein,
Oligomeric rings of the Sec61p complex induced by ligands required for protein translocation.
1996,
Pubmed
Harding,
Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase.
1999,
Pubmed
Haughey,
Involvement of inositol 1,4,5-trisphosphate-regulated stores of intracellular calcium in calcium dysregulation and neuron cell death caused by HIV-1 protein tat.
1999,
Pubmed
Hayashi,
Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival.
2007,
Pubmed
Hebert,
In and out of the ER: protein folding, quality control, degradation, and related human diseases.
2007,
Pubmed
Hetz,
Caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein.
2003,
Pubmed
Hofer,
ATP regulates calcium leak from agonist-sensitive internal calcium stores.
1996,
Pubmed
Kawaguchi,
Interplay of substrate retention and export signals in endoplasmic reticulum quality control.
2010,
Pubmed
Koumenis,
Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha.
2002,
Pubmed
Lang,
Sec61 complexes form ubiquitous ER Ca2+ leak channels.
2011,
Pubmed
Leissring,
Alzheimer's presenilin-1 mutation potentiates inositol 1,4,5-trisphosphate-mediated calcium signaling in Xenopus oocytes.
1999,
Pubmed
,
Xenbase
Li,
Ca2+-dependent redox modulation of SERCA 2b by ERp57.
2004,
Pubmed
,
Xenbase
Lin,
IRE1 signaling affects cell fate during the unfolded protein response.
2007,
Pubmed
Lindholm,
ER stress and neurodegenerative diseases.
2006,
Pubmed
Liu,
Ligand-independent dimerization activates the stress response kinases IRE1 and PERK in the lumen of the endoplasmic reticulum.
2000,
Pubmed
Lloyd,
A point mutation in Sec61alpha1 leads to diabetes and hepatosteatosis in mice.
2010,
Pubmed
Lodish,
Calcium is required for folding of newly made subunits of the asialoglycoprotein receptor within the endoplasmic reticulum.
1992,
Pubmed
Lomax,
Basal and physiological Ca(2+) leak from the endoplasmic reticulum of pancreatic acinar cells. Second messenger-activated channels and translocons.
2002,
Pubmed
Lytton,
Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca-ATPase family of calcium pumps.
1991,
Pubmed
Lytton,
Functional comparisons between isoforms of the sarcoplasmic or endoplasmic reticulum family of calcium pumps.
1992,
Pubmed
Mancini,
Multiple endoplasmic reticulum-associated pathways degrade mutant yeast carboxypeptidase Y in mammalian cells.
2003,
Pubmed
Marciniak,
CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum.
2004,
Pubmed
Meldolesi,
The endoplasmic reticulum Ca2+ store: a view from the lumen.
1998,
Pubmed
Nakagawa,
Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta.
2000,
Pubmed
Ong,
Intracellular Ca(2+) release via the ER translocon activates store-operated calcium entry.
2007,
Pubmed
Ozcan,
Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes.
2004,
Pubmed
Palmer,
Bcl-2-mediated alterations in endoplasmic reticulum Ca2+ analyzed with an improved genetically encoded fluorescent sensor.
2004,
Pubmed
Park,
Sarco(endo)plasmic reticulum Ca2+-ATPase 2b is a major regulator of endoplasmic reticulum stress and glucose homeostasis in obesity.
2010,
Pubmed
Pinton,
Reduced loading of intracellular Ca(2+) stores and downregulation of capacitative Ca(2+) influx in Bcl-2-overexpressing cells.
2000,
Pubmed
Prouty,
Multiphoton laser scanning microscopy as a tool for Xenopus oocyte research.
2006,
Pubmed
,
Xenbase
Roderick,
Cytosolic phosphorylation of calnexin controls intracellular Ca(2+) oscillations via an interaction with SERCA2b.
2000,
Pubmed
,
Xenbase
Schröder,
ER stress and the unfolded protein response.
2005,
Pubmed
Schäuble,
BiP-mediated closing of the Sec61 channel limits Ca2+ leakage from the ER.
2012,
Pubmed
Scorrano,
BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis.
2003,
Pubmed
Smith,
Hypoxic regulation of Ca2+ signaling in cultured rat astrocytes.
2005,
Pubmed
So,
Impaired endoplasmic reticulum stress response in B-lymphoblasts from patients with bipolar-I disorder.
2007,
Pubmed
Stutzmann,
Enhanced ryanodine receptor recruitment contributes to Ca2+ disruptions in young, adult, and aged Alzheimer's disease mice.
2006,
Pubmed
Swanton,
Protein folding and translocation across the endoplasmic reticulum membrane.
2003,
Pubmed
Tu,
Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations.
2006,
Pubmed
Van Coppenolle,
Ribosome-translocon complex mediates calcium leakage from endoplasmic reticulum stores.
2004,
Pubmed
Wang,
IL-1beta caused pancreatic beta-cells apoptosis is mediated in part by endoplasmic reticulum stress via the induction of endoplasmic reticulum Ca2+ release through the c-Jun N-terminal kinase pathway.
2009,
Pubmed
Wojda,
Calcium ions in neuronal degeneration.
2008,
Pubmed
Wong,
Inhibition of protein synthesis and early protein processing by thapsigargin in cultured cells.
1993,
Pubmed
Yoshida,
Depletion of intracellular Ca2+ store itself may be a major factor in thapsigargin-induced ER stress and apoptosis in PC12 cells.
2006,
Pubmed
Yoshida,
ER stress and diseases.
2007,
Pubmed
Zhao,
Endoplasmic reticulum stress in health and disease.
2006,
Pubmed
