Neuronal SOCE: Myth or Reality?

Lü, Bo; Fivaz, Marc

doi:10.1016/j.tcb.2016.09.008

Cited by 25 publications

(22 citation statements)

References 15 publications

(23 reference statements)

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“…However, our knowledge on neuronal SOCE (nSOCE) remains limited. In fact, the role of STIM proteins in this process is debated given the complex regulation of Ca 2+ inflow through various receptors and Ca 2+ channels [17][18][19]. nSOCE was identified in cortical, hippocampal, cerebellar, dorsal root ganglion, and dorsal horn neurons (reviewed in [19][20][21]) and shown to regulate synaptic plasticity, neurotransmitter release, and gene expression [22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

STIM Protein-NMDA2 Receptor Interaction Decreases NMDA-Dependent Calcium Levels in Cortical Neurons

Gruszczynska-Biegala

Strucinska

Maciąg

et al. 2020

Cells

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Neuronal Store-Operated Ca2+ Entry (nSOCE) plays an essential role in refilling endoplasmic reticulum Ca2+ stores and is critical for Ca2+-dependent neuronal processes. SOCE sensors, STIM1 and STIM2, can activate Orai, TRP channels and AMPA receptors, and inhibit voltage-gated channels in the plasma membrane. However, the link between STIM, SOCE, and NMDA receptors, another key cellular entry point for Ca2+ contributing to synaptic plasticity and excitotoxicity, remains unclear. Using Ca2+ imaging, we demonstrated that thapsigargin-induced nSOCE was inhibited in rat cortical neurons following NMDAR inhibitors. Blocking nSOCE by its inhibitor SKF96365 enhanced NMDA-driven [Ca2+]i. Modulating STIM protein level through overexpression or shRNA inhibited or activated NMDA-evoked [Ca2+]i, respectively. Using proximity ligation assays, immunofluorescence, and co-immunoprecipitation methods, we discovered that thapsigargin-dependent effects required interactions between STIMs and the NMDAR2 subunits. Since STIMs modulate NMDAR-mediated Ca2+ levels, we propose targeting this mechanism as a novel therapeutic strategy against neuropathological conditions that feature NMDA-induced Ca2+ overload as a diagnostic criterion.

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Section: Introductionmentioning

confidence: 99%

STIM Protein-NMDA2 Receptor Interaction Decreases NMDA-Dependent Calcium Levels in Cortical Neurons

Gruszczynska-Biegala

Strucinska

Maciąg

et al. 2020

Cells

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“…This difference could arise from the protocols used to measure SOCE activity in neurons. In this study, ER-Ca 2+ depletion was triggered in a medium containing physiological calcium concentration, while Gruszczynska-Biegala et al ( 2016 ) employed the Ca 2+ addback protocol, in which addition of Ca 2+ to the external medium may activate neuronal Ca 2+ channels by changing the membrane excitability as described elsewhere (Lu and Fivaz, 2016 ).…”

Section: Resultsmentioning

confidence: 99%

“…This mechanism is called store-operated calcium entry (SOCE; Putney, 1986 ), and it has been extensively studied in non-excitable cells, for which SOCE acts as a principal Ca 2+ entry pathway (Parekh and Putney, 2005 ; Prakriya and Lewis, 2015 ). Conversely, the relevance of neuronal SOCE is being debated (Lu and Fivaz, 2016 ). In the last few years, SOCE activity has been observed in hippocampal (Emptage et al, 2001 ; Baba et al, 2003 ; Kann et al, 2012 ; Sun et al, 2014 ; Samtleben et al, 2015 ), cortical (Berna-Erro et al, 2009 ; Klejman et al, 2009 ; Gruszczynska-Biegala et al, 2011 ), cerebellar (Baba et al, 2003 ; Hartmann et al, 2014 ), sensory (Gemes et al, 2011 ) and dorsal horn neurons (Xia et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Store-Operated Calcium Entry Is Required for mGluR-Dependent Long Term Depression in Cortical Neurons

González-Sánchez

Arco

Esteban

et al. 2017

Front. Cell. Neurosci.

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Store-operated calcium entry (SOCE) is a Calcium (Ca2+) influx pathway activated by depletion of intracellular stores that occurs in eukaryotic cells. In neurons, the presence and functions of SOCE are still in question. Here, we show evidences for the existence of SOCE in primary mouse cortical neurons. Endoplasmic reticulum (ER)-Ca2+ depletion using thapsigargin (Tg) triggered a maintained cytosolic Ca2+ increase, which rapidly returned to basal level in the presence of the SOCE blockers 2-Aminoethoxydiphenyl borate (2-APB) and YM-58483. Neural SOCE is also engaged by activation of metabotropic glutamate receptors (mGluRs) with (S)-3,5-dihydroxyphenylglycine (DHPG) (agonist of group I mGluRs), being an essential mechanism to maintain the mGluR-driven Ca2+ signal. Activation of group I of mGluRs triggers long-term depression (LTD) in many brain regions, but the underlying mechanism and, specifically, the necessity of Ca2+ increase in the postsynaptic neuron is controversial. In primary cortical neurons, we now show that the inhibition of Ca2+ influx through SOCE impaired DHPG-LTD, pointing out a key function of calcium and SOCE in synaptic plasticity.

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“…). In the nervous system, STIM2 seems to have the predominant function, and despite the presence of SOCE in this tissue, this function is not clear (for review see Lu & Fivaz, ), and the tendency is to accept the existence of a particular version of SOCE in neurons. Interestingly, groups that used constitutive knockout mice for these studies showed significant results, while those that used conditional knockout mice observed irrelevant results.…”

Section: Introductionmentioning

confidence: 99%

Role of STIM2 in cell function and physiopathology

Berna‐Erro

Jardín

Salido

et al. 2017

The Journal of Physiology

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An endoplasmic reticulum (ER)-resident protein that regulates cytosolic and ER free-Ca concentration by induction of store-operated calcium entry: that is the original definition of STIM2 and its function. While its activity strongly depends on the amount of calcium stored in the ER, its function goes further, to intracellular signalling and gene expression. Initially under-studied owing to the prominent function of STIM1, STIM2 came to be regarded as vital in mice, gradually emerging as an important player in the nervous system, and cooperating with STIM1 in the immune system. STIM2 has also been proposed as a relevant player in pathological conditions related to ageing, Alzheimer's and Huntington's diseases, autoimmune disorders and cancer. The discovery of additional functions, together with new splicing forms with opposite roles, has clarified existing controversies about STIM2 function in SOCE. With STIM2 being essential for life, but apparently not for development, newly available data demonstrate a complex and still intriguing behaviour that this review summarizes, updating current knowledge of STIM2 function.

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Neuronal SOCE: Myth or Reality?

Cited by 25 publications

References 15 publications

STIM Protein-NMDA2 Receptor Interaction Decreases NMDA-Dependent Calcium Levels in Cortical Neurons

STIM Protein-NMDA2 Receptor Interaction Decreases NMDA-Dependent Calcium Levels in Cortical Neurons

Store-Operated Calcium Entry Is Required for mGluR-Dependent Long Term Depression in Cortical Neurons

Role of STIM2 in cell function and physiopathology

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