Stim and Orai proteins in neuronal Ca2+ signalling and excitability
Stim1 and Orai1 are ubiquitous proteins that have long been known to mediate Ca2+ release-activated Ca2+ (CRAC) current (ICRAC) and store-operated Ca2+ entry (SOCE) only in non-excitable cells. SOCE is activated following the depletion of the endogenous Ca2+ stores, which are mainly located within t...
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doaj-f32e2b4f84fd44ce938d5809a2ee141c2020-11-24T21:09:29ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022015-04-01910.3389/fncel.2015.00153137798Stim and Orai proteins in neuronal Ca2+ signalling and excitabilityFrancesco eMoccia0Estella eZuccolo1Teresa eSoda2Franco eTanzi3Germano eGuerra4Lisa eMapelli5Lisa eMapelli6Francesco eLodola7Egidio eD‘Angelo8Egidio eD‘Angelo9University of PaviaUniversity of PaviaUniversity of PaviaUniversity of PaviaUniversity of MoliseUniversity of PaviaMuseo Storico della Fisica e Centro Studi e Ricerche Enrico FermiIRCCS Fondazione Salvatore MaugeriUniversity of PaviaC. Mondino National Neurological Institute, IRCCS PaviaStim1 and Orai1 are ubiquitous proteins that have long been known to mediate Ca2+ release-activated Ca2+ (CRAC) current (ICRAC) and store-operated Ca2+ entry (SOCE) only in non-excitable cells. SOCE is activated following the depletion of the endogenous Ca2+ stores, which are mainly located within the endoplasmic reticulum (ER), to replete the intracellular Ca2+ reservoir and engage specific Ca2+-dependent processes, such as proliferation, migration, cytoskeletal remodelling, and gene expression. Their paralogues, Stim2, Orai2 and Orai3, support SOCE in heterologous expression systems, but their physiological role is still obscure. Ca2+ inflow in neurons has long been exclusively ascribed to voltage-operated and receptor-operated channels. Nevertheless, recent work has unveiled that Stim1-2 and Orai1-2, but not Orai3, proteins are also expressed and mediate SOCE in neurons. Herein, we survey current knowledge about the neuronal distribution of Stim and Orai proteins in rodent and human brains; we further discuss that Orai2 is the main pore-forming subunit of CRAC channels in central neurons, in which it may be activated by either Stim1 or Stim2 depending on species, brain region and physiological stimuli. We examine the functions regulated by SOCE in neurons, where this pathway is activated under resting conditions to refill the ER, control spinogenesis and regulate gene transcription. Besides, we highlighted the possibility that SOCE also controls neuronal excitation and regulate synaptic plasticity. Finally, we evaluate the involvement of Stim and Orai proteins in severe neurodegenerative and neurological disorders, such as Alzheimer’s Disease and epilepsy.http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00153/fullNeuronsstore-operated Ca2+ entryCa2+ signalingOrai1STIM1STIM2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Francesco eMoccia Estella eZuccolo Teresa eSoda Franco eTanzi Germano eGuerra Lisa eMapelli Lisa eMapelli Francesco eLodola Egidio eD‘Angelo Egidio eD‘Angelo |
spellingShingle |
Francesco eMoccia Estella eZuccolo Teresa eSoda Franco eTanzi Germano eGuerra Lisa eMapelli Lisa eMapelli Francesco eLodola Egidio eD‘Angelo Egidio eD‘Angelo Stim and Orai proteins in neuronal Ca2+ signalling and excitability Frontiers in Cellular Neuroscience Neurons store-operated Ca2+ entry Ca2+ signaling Orai1 STIM1 STIM2 |
author_facet |
Francesco eMoccia Estella eZuccolo Teresa eSoda Franco eTanzi Germano eGuerra Lisa eMapelli Lisa eMapelli Francesco eLodola Egidio eD‘Angelo Egidio eD‘Angelo |
author_sort |
Francesco eMoccia |
title |
Stim and Orai proteins in neuronal Ca2+ signalling and excitability |
title_short |
Stim and Orai proteins in neuronal Ca2+ signalling and excitability |
title_full |
Stim and Orai proteins in neuronal Ca2+ signalling and excitability |
title_fullStr |
Stim and Orai proteins in neuronal Ca2+ signalling and excitability |
title_full_unstemmed |
Stim and Orai proteins in neuronal Ca2+ signalling and excitability |
title_sort |
stim and orai proteins in neuronal ca2+ signalling and excitability |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular Neuroscience |
issn |
1662-5102 |
publishDate |
2015-04-01 |
description |
Stim1 and Orai1 are ubiquitous proteins that have long been known to mediate Ca2+ release-activated Ca2+ (CRAC) current (ICRAC) and store-operated Ca2+ entry (SOCE) only in non-excitable cells. SOCE is activated following the depletion of the endogenous Ca2+ stores, which are mainly located within the endoplasmic reticulum (ER), to replete the intracellular Ca2+ reservoir and engage specific Ca2+-dependent processes, such as proliferation, migration, cytoskeletal remodelling, and gene expression. Their paralogues, Stim2, Orai2 and Orai3, support SOCE in heterologous expression systems, but their physiological role is still obscure. Ca2+ inflow in neurons has long been exclusively ascribed to voltage-operated and receptor-operated channels. Nevertheless, recent work has unveiled that Stim1-2 and Orai1-2, but not Orai3, proteins are also expressed and mediate SOCE in neurons. Herein, we survey current knowledge about the neuronal distribution of Stim and Orai proteins in rodent and human brains; we further discuss that Orai2 is the main pore-forming subunit of CRAC channels in central neurons, in which it may be activated by either Stim1 or Stim2 depending on species, brain region and physiological stimuli. We examine the functions regulated by SOCE in neurons, where this pathway is activated under resting conditions to refill the ER, control spinogenesis and regulate gene transcription. Besides, we highlighted the possibility that SOCE also controls neuronal excitation and regulate synaptic plasticity. Finally, we evaluate the involvement of Stim and Orai proteins in severe neurodegenerative and neurological disorders, such as Alzheimer’s Disease and epilepsy. |
topic |
Neurons store-operated Ca2+ entry Ca2+ signaling Orai1 STIM1 STIM2 |
url |
http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00153/full |
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