A calcium-accumulating region, CAR, in the channel Orai1 enhances Ca 2+ permeation and SOCE-induced gene transcription DOI
Irene Frischauf, Vasilina Zayats,

Michael Deix

et al.

Science Signaling, Journal Year: 2015, Volume and Issue: 8(408)

Published: Dec. 22, 2015

The Ca(2+) release-activated channel mediates influx in a plethora of cell types, thereby controlling diverse cellular functions. complex is composed stromal interaction molecule 1 (STIM1), an endoplasmic reticulum Ca(2+)-sensing protein, and Orai1, plasma membrane channel. Channels STIM1 Orai1 mediate even at low extracellular concentrations. We investigated whether the activity adapted to different environmental used homology modeling molecular dynamics simulations predict presence Ca(2+)-accumulating region (CAR) pore entrance Orai1. Furthermore, proteins with mutations CAR, along live-cell experiments, or electrophysiological recordings transient, electrostatic loop3 interacting loop1 (the site CAR) determined that CAR enhanced permeation most efficiently external Consistent these results, cells expressing mutants exhibited impaired gene expression stimulated by Ca(2+)-activated transcription factor nuclear activated T (NFAT). propose architecture close proximity selectivity filter, which enables Ca(2+)-selective ion permeation, enhances local concentration maintain Ca(2+)-dependent regulation environments relatively Ca(2+)concentrations.

Language: Английский

The calcium–cancer signalling nexus DOI
Gregory R. Monteith, Natalia Prevarskaya, Sarah J. Roberts‐Thomson

et al.

Nature reviews. Cancer, Journal Year: 2017, Volume and Issue: 17(6), P. 373 - 380

Published: April 7, 2017

Language: Английский

Citations

501

The coming of age of the mitochondria–ER contact: a matter of thickness DOI Open Access
Marta Giacomello, Luca Pellegrini

Cell Death and Differentiation, Journal Year: 2016, Volume and Issue: 23(9), P. 1417 - 1427

Published: June 24, 2016

Language: Английский

Citations

373

NFAT control of immune function: New Frontiers for an Abiding Trooper DOI Creative Commons
Martin Vaeth, Stefan Feske

F1000Research, Journal Year: 2018, Volume and Issue: 7, P. 260 - 260

Published: March 2, 2018

Nuclear factor of activated T cells (NFAT) was first described almost three decades ago as a Ca2+/calcineurin-regulated transcription in cells. Since then, large body research uncovered the regulation and physiological function different NFAT homologues immune system many other tissues. In this review, we will discuss novel roles cells, focusing mainly on its humoral responses, immunological tolerance, metabolism.

Language: Английский

Citations

175

Calcium signaling and the therapeutic targeting of cancer cells DOI Creative Commons
Alice H. L. Bong, Gregory R. Monteith

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2018, Volume and Issue: 1865(11), P. 1786 - 1794

Published: May 26, 2018

Language: Английский

Citations

167

CRAC Channels and Calcium Signaling in T Cell-Mediated Immunity DOI
Martin Vaeth, Sascha Kahlfuß, Stefan Feske

et al.

Trends in Immunology, Journal Year: 2020, Volume and Issue: 41(10), P. 878 - 901

Published: July 22, 2020

Language: Английский

Citations

158

Molecular mechanisms of STIM/Orai communication DOI Creative Commons
Isabella Derler, Isaac Jardín, Christoph Romanin

et al.

AJP Cell Physiology, Journal Year: 2016, Volume and Issue: 310(8), P. C643 - C662

Published: Jan. 30, 2016

Ca(2+)entry into the cell via store-operated Ca(2+)release-activated Ca(2+)(CRAC) channels triggers diverse signaling cascades that affect cellular processes like growth, gene regulation, secretion, and death. These Ca(2+)channels open after depletion of intracellular Ca(2+)stores, their main features are fully reconstituted by two molecular key players: stromal interaction molecule (STIM) Orai. STIM represents an endoplasmic reticulum-located Ca(2+)sensor, while Orai forms a highly Ca(2+)-selective ion channel in plasma membrane. Functional as well mutagenesis studies together with structural insights about proteins provide picture interplay these players CRAC cascade. This review focuses on experimental advances understanding STIM1-Orai choreography, thereby establishing portrait mechanistic steps The focus is activation proteins, subsequent coupling STIM1 to Orai1, consequent rearrangements gate state allow Ca(2+)permeation cell.

Language: Английский

Citations

125

Ion channelopathies of the immune system DOI
Martin Vaeth, Stefan Feske

Current Opinion in Immunology, Journal Year: 2018, Volume and Issue: 52, P. 39 - 50

Published: April 7, 2018

Language: Английский

Citations

120

Calcineurin signaling in the heart: The importance of time and place DOI
Valentina Parra, Beverly A. Rothermel

Journal of Molecular and Cellular Cardiology, Journal Year: 2016, Volume and Issue: 103, P. 121 - 136

Published: Dec. 20, 2016

Language: Английский

Citations

92

The Calcium-Signaling Toolkit in Cancer: Remodeling and Targeting DOI Open Access
Sarah J. Roberts‐Thomson, Silke B. Chalmers, Gregory R. Monteith

et al.

Cold Spring Harbor Perspectives in Biology, Journal Year: 2019, Volume and Issue: 11(8), P. a035204 - a035204

Published: May 14, 2019

Processes that are important in cancer progression, such as sustained cell growth, invasion to other organs, and resistance death inducers, have a clear overlap with pathways regulated by Ca2+ signaling. It is therefore not surprising proteins signaling, sometimes referred the "Ca2+ signaling toolkit," can contribute proliferation invasiveness, ability of agents induce death. also critical aspects including events tumor microenvironment processes involved acquisition anticancer therapies. This review will consider role progression highlight areas which better understanding interplay between Ca2+-signaling toolkit tumorigenesis still required.

Language: Английский

Citations

85

Synthetic gene networks recapitulate dynamic signal decoding and differential gene expression DOI Creative Commons
Dirk Benzinger, Serguei Ovinnikov, Mustafa Khammash

et al.

Cell Systems, Journal Year: 2022, Volume and Issue: 13(5), P. 353 - 364.e6

Published: March 16, 2022

Language: Английский

Citations

42