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.
J Biol Chem
2011 Aug 12;28632:27947-58. doi: 10.1074/jbc.M111.226738.
Show Gene links
Show Anatomy links
Sig1R protein regulates hERG channel expression through a post-translational mechanism in leukemic cells.
Crottès D
,
Martial S
,
Rapetti-Mauss R
,
Pisani DF
,
Loriol C
,
Pellissier B
,
Martin P
,
Chevet E
,
Borgese F
,
Soriani O
.
???displayArticle.abstract???
Sig1R (Sigma-1receptor) is a 25-kDa protein structurally unrelated to other mammalian proteins. Sig1R is present in brain, liver, and heart and is overexpressed in cancer cells. Studies using exogenous sigma ligands have shown that Sig1R interacts with a variety of ion channels, but its intrinsic function and mechanism of action remain unclear. The human ether-à-gogo related gene (hERG) encodes a cardiac channel that is also abnormally expressed in many primary human cancers, potentiating tumor progression through the modulation of extracellular matrix adhesive interactions. We show herein that sigma ligands inhibit hERG current density and cell adhesion to fibronectin in K562 myeloid leukemia cells. Heterologous expression in Xenopus oocytes demonstrates that Sig1R potentiates hERG current by stimulating channel subunit biosynthesis. Silencing Sig1R in leukemic K562 cells depresses hERG current density and cell adhesion to fibronectin by reducing hERG membrane expression. In K562 cells, Sig1R silencing does not modify hERG mRNA contents but reduces hERG mature form densities. In HEK cells expressing hERG and Sig1R, both proteins co-immunoprecipitate, demonstrating a physical association. Finally, Sig1R expression enhances both channel protein maturation and stability. Altogether, these results demonstrate for the first time that Sig1R controls ion channel expression through the regulation of subunit trafficking activity.
Albagli-Curiel,
A new generation of pPRIG-based retroviral vectors.
2007, Pubmed
Albagli-Curiel,
A new generation of pPRIG-based retroviral vectors.
2007,
Pubmed
Aydar,
The sigma receptor as a ligand-regulated auxiliary potassium channel subunit.
2002,
Pubmed
,
Xenbase
Cameron,
Calnexin phosphorylation attenuates the release of partially misfolded alpha1-antitrypsin to the secretory pathway.
2009,
Pubmed
Carnally,
Demonstration of a direct interaction between sigma-1 receptors and acid-sensing ion channels.
2010,
Pubmed
Cavarra,
HERG1 currents in native K562 leukemic cells.
2007,
Pubmed
Cherubini,
Human ether-a-go-go-related gene 1 channels are physically linked to beta1 integrins and modulate adhesion-dependent signaling.
2005,
Pubmed
Downie,
Eag1 expression interferes with hypoxia homeostasis and induces angiogenesis in tumors.
2008,
Pubmed
Ficker,
Role of the cytosolic chaperones Hsp70 and Hsp90 in maturation of the cardiac potassium channel HERG.
2003,
Pubmed
Fontanilla,
The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator.
2009,
Pubmed
Fraser,
Ion channels: functional expression and therapeutic potential in cancer. Colloquium on Ion Channels and Cancer.
2008,
Pubmed
Ganapathi,
Ceramide modulates HERG potassium channel gating by translocation into lipid rafts.
2010,
Pubmed
Guasti,
Identification of a posttranslational mechanism for the regulation of hERG1 K+ channel expression and hERG1 current density in tumor cells.
2008,
Pubmed
Guizouarn,
Point mutations involved in red cell stomatocytosis convert the electroneutral anion exchanger 1 to a nonselective cation conductance.
2007,
Pubmed
,
Xenbase
Guo,
Extracellular K+ concentration controls cell surface density of IKr in rabbit hearts and of the HERG channel in human cell lines.
2009,
Pubmed
Hanner,
Purification, molecular cloning, and expression of the mammalian sigma1-binding site.
1996,
Pubmed
Hayashi,
Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival.
2007,
Pubmed
Hayashi,
Intracellular dynamics of sigma-1 receptors (sigma(1) binding sites) in NG108-15 cells.
2003,
Pubmed
Herrera,
sigma-1 receptor modulation of acid-sensing ion channel a (ASIC1a) and ASIC1a-induced Ca2+ influx in rat cortical neurons.
2008,
Pubmed
Hofmann,
HERG K+ channels activation during beta(1) integrin-mediated adhesion to fibronectin induces an up-regulation of alpha(v)beta(3) integrin in the preosteoclastic leukemia cell line FLG 29.1.
2001,
Pubmed
Jones,
Cardiac IKr channels minimally comprise hERG 1a and 1b subunits.
2004,
Pubmed
Le Guennec,
Voltage-gated ion channels, new targets in anti-cancer research.
2007,
Pubmed
Mavlyutov,
The sigma-1 receptor is enriched in postsynaptic sites of C-terminals in mouse motoneurons. An anatomical and behavioral study.
2010,
Pubmed
Mavlyutov,
Ligand-dependent localization and intracellular stability of sigma-1 receptors in CHO-K1 cells.
2007,
Pubmed
McDonald,
A minK-HERG complex regulates the cardiac potassium current I(Kr).
1997,
Pubmed
,
Xenbase
Meng,
Evidence for the presence of a low-mass beta1 integrin on the cell surface.
2005,
Pubmed
Monnet,
The sigma1 protein as a target for the non-genomic effects of neuro(active)steroids: molecular, physiological, and behavioral aspects.
2006,
Pubmed
Morin-Surun,
Intracellular sigma1 receptor modulates phospholipase C and protein kinase C activities in the brainstem.
1999,
Pubmed
Palmer,
Sigma-1 receptors bind cholesterol and remodel lipid rafts in breast cancer cell lines.
2007,
Pubmed
Petrecca,
N-linked glycosylation sites determine HERG channel surface membrane expression.
1999,
Pubmed
Phartiyal,
Endoplasmic reticulum retention and rescue by heteromeric assembly regulate human ERG 1a/1b surface channel composition.
2008,
Pubmed
,
Xenbase
Pillozzi,
VEGFR-1 (FLT-1), beta1 integrin, and hERG K+ channel for a macromolecular signaling complex in acute myeloid leukemia: role in cell migration and clinical outcome.
2007,
Pubmed
Pillozzi,
Physical and functional interaction between integrins and hERG1 channels in cancer cells.
2010,
Pubmed
Pillozzi,
Chemotherapy resistance in acute lymphoblastic leukemia requires hERG1 channels and is overcome by hERG1 blockers.
2011,
Pubmed
Prevarskaya,
Ion channels and the hallmarks of cancer.
2010,
Pubmed
Renaudo,
Cancer cell cycle modulated by a functional coupling between sigma-1 receptors and Cl- channels.
2007,
Pubmed
Renaudo,
Inhibition of tumor cell proliferation by sigma ligands is associated with K+ Channel inhibition and p27kip1 accumulation.
2004,
Pubmed
Roman,
JO 1784, a potent and selective ligand for rat and mouse brain sigma-sites.
1990,
Pubmed
Sale,
Physiological properties of hERG 1a/1b heteromeric currents and a hERG 1b-specific mutation associated with Long-QT syndrome.
2008,
Pubmed
Sanguinetti,
Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents.
1990,
Pubmed
Sanguinetti,
A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel.
1995,
Pubmed
,
Xenbase
Soriani,
Sigma ligands stimulate the electrical activity of frog pituitary melanotrope cells through a G-protein-dependent inhibition of potassium conductances.
1998,
Pubmed
Soriani,
A-Current down-modulated by sigma receptor in frog pituitary melanotrope cells through a G protein-dependent pathway.
1999,
Pubmed
Soriani,
The sigma-ligand (+)-pentazocine depresses M current and enhances calcium conductances in frog melanotrophs.
1999,
Pubmed
Spruce,
Small molecule antagonists of the sigma-1 receptor cause selective release of the death program in tumor and self-reliant cells and inhibit tumor growth in vitro and in vivo.
2004,
Pubmed
Su,
The sigma-1 receptor chaperone as an inter-organelle signaling modulator.
2010,
Pubmed
Trudeau,
HERG, a human inward rectifier in the voltage-gated potassium channel family.
1995,
Pubmed
Tsai,
Sigma-1 receptor chaperones and diseases.
2009,
Pubmed
Vernon-Wilson,
CD31 delays phagocyte membrane repolarization to promote efficient binding of apoptotic cells.
2007,
Pubmed
