Molecular mechanisms of STIM/Orai communication

AJP Cell Physiology, Год журнала: 2016, Номер 310(8), С. C643 - C662

Опубликована: Янв. 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.

Язык: Английский

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Store-Operated Calcium Channels: From Function to Structure and Back Again

Cold Spring Harbor Perspectives in Biology, Год журнала: 2019, Номер 12(5), С. a035055 - a035055

Опубликована: Сен. 30, 2019

Richard S. Lewis Department of Molecular and Cellular Physiology, Stanford University School Medicine, Stanford, California 94305 Correspondence: rslewis{at}stanford.edu

Язык: Английский

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The Orai1 Store-operated Calcium Channel Functions as a Hexamer

Journal of Biological Chemistry, Год журнала: 2016, Номер 291(50), С. 25764 - 25775

Опубликована: Окт. 26, 2016

Язык: Английский

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Mitochondria control store‐operated Ca ²⁺ entry through Na ⁺ and redox signals

The EMBO Journal, Год журнала: 2017, Номер 36(6), С. 797 - 815

Опубликована: Фев. 20, 2017

Язык: Английский

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STIM1 activation of Orai1

Cell Calcium, Год журнала: 2018, Номер 77, С. 29 - 38

Опубликована: Ноя. 30, 2018

A primary calcium (Ca2+) entry pathway into non-excitable cells is through the store-operated Ca2+ release activated (CRAC) channel. responsible for initiation of diverse signalling cascades that affect essential cellular processes like gene regulation, cell growth and death, secretion transcription. Upon depletion intracellular stores within endoplasmic reticulum (ER), CRAC channel opens to refill depleted stores. The two key limiting molecular players are stromal interaction molecule (STIM1) embedded in ER-membrane Orai1, residing plasma membrane (PM), respectively. Together, they form a highly selective ion complex. STIM1 senses content ER confers store-depletion opening Orai1 channels PM triggering Ca2+-dependent transcription, T-cell activation or mast degranulation. interplay Orai STIM proteins cascade has been main focus research more than twelve years. This chapter focuses on current knowledge experimental advances understanding by STIM1, thereby portraying mechanistic steps cascade.

Язык: Английский

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The STIM1-binding site nexus remotely controls Orai1 channel gating

Nature Communications, Год журнала: 2016, Номер 7(1)

Опубликована: Дек. 8, 2016

Abstract The ubiquitously expressed Orai Ca 2+ channels are gated through a unique process of intermembrane coupling with the -sensing STIM proteins. Despite significance Orai1-mediated signals, how gating Orai1 is triggered by STIM1 remains unknown. A widely held model invokes binding directly to pore-forming helix. Here we report that an C-terminal STIM1-binding site, situated far from N-terminal pore helix, alone provides trigger necessary and sufficient for channel gating. We identify critical ‘nexus’ within connecting peripheral site core helices. Mutation nexus transforms into persistently open state exactly mimicking action STIM1. suggest transduces signal conformational change in inner helices, remotely gates without necessity direct contact

Язык: Английский

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The STIM-Orai coupling interface and gating of the Orai1 channel

Cell Calcium, Год журнала: 2017, Номер 63, С. 8 - 13

Опубликована: Янв. 8, 2017

Язык: Английский

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Cross-linking of Orai1 channels by STIM proteins

Proceedings of the National Academy of Sciences, Год журнала: 2018, Номер 115(15)

Опубликована: Март 26, 2018

Significance The work presents a unique understanding of the organization and function two ubiquitously expressed proteins, central in generating calcium signals all cell types. These are intracellular sensing “STIM” highly selective surface “Orai” channels. We reveal that STIM proteins can cross-link Orai channels, resulting reorganized microenvironment within membrane junctions which they function, with important consequences generation oscillatory signals. Interestingly, we show variant protein widely cells functions to prevent STIM–Orai cross-linking clustering This provides modulation signal serve protect from overstimulation signaling machinery.

Язык: Английский

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STIM-Orai Channels and Reactive Oxygen Species in the Tumor Microenvironment

Cancers, Год журнала: 2019, Номер 11(4), С. 457 - 457

Опубликована: Март 30, 2019

The tumor microenvironment (TME) is shaped by cancer and noncancerous cells, the extracellular matrix, soluble factors, blood vessels. Interactions between vessels generate this complex heterogeneous microenvironment. TME may be metabolically beneficial or unbeneficial for growth, it favor not a productive immune response against even conditions suited to hijacking system benefitting growth. Soluble factors relevant include oxygen, reactive oxygen species (ROS), ATP, Ca2+, H+, growth cytokines. Ca2+ plays prominent role in because its concentration directly linked cell proliferation, apoptosis, migration but also function. Stromal-interaction molecules (STIM)-activated Orai channels are major entry cells they upregulated many tumors, strongly regulated ROS. Thus, STIM interesting candidates regulate fate TME. In review, we summarize current knowledge about function of ROS STIM/Orai cells; discuss their interdependencies; propose new hypotheses how TME, ROS, influence each other.

Язык: Английский

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STIM1-dependent peripheral coupling governs the contractility of vascular smooth muscle cells

eLife, Год журнала: 2022, Номер 11

Опубликована: Фев. 11, 2022

Peripheral coupling between the sarcoplasmic reticulum (SR) and plasma membrane (PM) forms signaling complexes that regulate potential contractility of vascular smooth muscle cells (VSMCs). The mechanisms responsible for these interactions are poorly understood. In many cells, STIM1 (stromal interaction molecule 1), a single-transmembrane-domain protein resides in endoplasmic (ER), transiently moves to ER-PM junctions response depletion ER Ca 2+ stores initiates store-operated entry (SOCE). Fully differentiated VSMCs express but exhibit only marginal SOCE activity. We hypothesized is constitutively active contractile maintains peripheral coupling. support this concept, we found number size SR-PM interacting sites were decreased, SR-dependent -signaling processes disrupted freshly isolated cerebral artery SMCs from tamoxifen-inducible, SMC-specific STIM1-knockout ( Stim1- smKO) mice. smKO mice also exhibited reduction nanoscale colocalization -release on SR -activated ion channels PM, accompanied by diminished channel hypotensive, resistance arteries them displayed blunted contractility. These data suggest – independent store critically important stable VSMCs.

Язык: Английский

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