Store-operated calcium entry compensates fast ER calcium loss in resting hippocampal neurons

There are growing indications for the involvement of calcium stores in the plastic properties of neurons and particularly in dendritic spines of central neurons. The store-operated calcium entry (SOCE) channels are assumed to be activated by the calcium sensor stromal interaction molecule (STIM)which leads to activation of its associated Orai channel. There are two STIM species, and the differential role of the two in SOCE is not entirely clear. In the present study, we were able to distinguish between transfected STIM1, which is more mobile primarily in young neurons, and STIM2 which is less mobile and more prominent in older neurons in culture. STIM1 mobility is associated with spontaneous calcium sparks, local transient rise in cytosolic [Ca2+]i, and in the formation and elongation of dendritic filopodia/spines. In contrast, STIM2 is associated with older neurons, where it is mobile and moves into dendritic spines primarily when cytosolic [Ca2+]i levels are reduced, apparently to activate resident Orai channels. These results highlight a role for STIM1 in the regulation of [Ca2+]i fluctuations associated with the formation of dendritic spines or filopodia in the developing neuron, whereas STIM2 is associated with the maintenance of calcium entry into stores in the adult neuron.

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Store-operated calcium entry in physiology and pathology of mammalian cells.

Acta Biochimica Polonica ◽

10.18388/abp.2005_3452 ◽

2005 ◽

Vol 52 (2) ◽

pp. 397-409 ◽

Cited By ~ 40

Author(s):

Berenika Targos ◽

Jolanta Barańska ◽

Paweł Pomorski

Keyword(s):

Cell Cycle ◽

Calcium Level ◽

Mammalian Cells ◽

Long Term Potentiation ◽

Calcium Entry ◽

Neuroendocrine Cells ◽

Calcium Stores ◽

Excitable Cells ◽

Store Operated Calcium Entry ◽

Er Calcium

One of the numerous calcium-involving processes in mammalian cells is store-operated calcium entry (SOCE) -- the process in which depletion of calcium stores in the endoplasmic reticulum (ER) induces calcium influx from the extracellular space. Previously supposed to function only in non-excitable cells, SOCE is now known to play a role also in such excitable cells as neurons, muscles and neuroendocrine cells and is found in many different cell types. SOCE participates not only in processes dependent on ER calcium level but also specifically regulates some important processes such as cAMP production, T lymphocyte activation or induction of long-term potentiation. Impairment of SOCE can be an element of numerous disorders such as acute pancreatitis, primary immunodeficiency and, since it can take part in apoptosis or cell cycle regulation, SOCE may also be partially responsible for such serious disorders as Alzheimer disease and many types of cancer. Even disturbances in the 'servant' role of maintaining ER calcium level may cause serious effects because they can lead to ER homeostasis disturbance, influencing gene expression, protein synthesis and processing, and the cell cycle.

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Impairment of Store-operated Calcium Entry: Implications in Alzheimer’s Neurodegeneration

Current Alzheimer Research ◽

10.2174/1567205018666210119144241 ◽

2021 ◽

Vol 17 (12) ◽

pp. 1088-1094

Author(s):

Jing Zhou ◽

Shengzhou Wu

Keyword(s):

Endoplasmic Reticulum ◽

Neurodegenerative Disorder ◽

Therapeutic Potential ◽

Alternative Hypothesis ◽

Cholinergic Neurons ◽

Proteasome Inhibition ◽

Calcium Entry ◽

Calcium Sensors ◽

Store Operated Calcium Entry ◽

Er Calcium

Alzheimer's disease (AD) is an insidious and progressive neurodegenerative disorder. Dysfunction of central cholinergic neurons, amyloid aggregation and deposition,oxidative stress,and biometal dyshomeostasis has been regarded as the major pathogenic mediators in this devastating disease. However, strategies derived from these hypotheses fail to slow down or stop the progression of AD, warranting a combination of therapies to target multiple etiological factors or examining alternative hypothesis. Store-operated calcium entry (SOCE) is the process by which depletion of calcium in the endoplasmic reticulum (ER) lumen causes an influx of calcium across plasmalemma. Accumulating evidence indicates that neuronal SOCE (nSOCE) is inhibited in family AD (FAD) and the inhibition of which causes instability of dendritic spines and enhances amyloidogenesis. Mutant Presenilin fails to function as an ER calcium leak channel and promotes degradation of stromal interaction molecules (STIM), ER calcium sensors; these effects may account for the repression of nSOCE in FAD. We have demonstrated that activation of autophagy degrades STIM proteins, resulting in a trimming effect on a dendritic arbor, under proteasome inhibition and endoplasmic reticulum stress, which are intimately connected with AD. Thus, we hypothesize that autophagy represses SOCE by degrading STIM proteins, leading to synapse loss in AD. This review article will highlight the roles of SOCE in AD neurodegeneration, the degradative mechanisms of STIM protein, and the therapeutic potential and associated challenge.

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2074-P: Histone Deacetylase Inhibitors Improve Store-Operated Calcium Entry and Glucose-Stimulated Insulin Secretion in Cytokine-Stressed Pancreatic ß-Cells

Diabetes ◽

10.2337/db20-2074-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 2074-P

Author(s):

CHIH-CHUN LEE ◽

TATSUYOSHI KONO ◽

STACI A. WEAVER ◽

PAUL SOHN ◽

CARMELLA EVANS-MOLINA

Keyword(s):

Insulin Secretion ◽

Histone Deacetylase ◽

Histone Deacetylase Inhibitors ◽

Calcium Entry ◽

Store Operated Calcium Entry ◽

Glucose Stimulated Insulin Secretion

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A CRITICAL ROLE OF TRPC1-ORAI1-STIM1 MEDIATED STORE OPERATED CALCIUM ENTRY IN CARDIAC HYPERTROPHY

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(15)60902-0 ◽

2015 ◽

Vol 65 (10) ◽

pp. A902

Author(s):

Senthil Selvaraj ◽

Brij Singh ◽

Christian Bollensdorff ◽

Jassim Al Suwaidi ◽

Magdi Yacoub

Keyword(s):

Cardiac Hypertrophy ◽

Critical Role ◽

Calcium Entry ◽

Store Operated Calcium Entry

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Synthesis and Characterization of Store-Operated Calcium Entry Inhibitors Active in the Submicromolar Range

International Journal of Molecular Sciences ◽

10.3390/ijms21249777 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9777

Author(s):

Camille Le Guilcher ◽

Tomas Luyten ◽

Jan B. Parys ◽

Mathieu Pucheault ◽

Olivier Dellis

Keyword(s):

Cell Activation ◽

Interleukin 2 ◽

Calcium Entry ◽

Ip3 Receptors ◽

Excitable Cells ◽

Cellular Targets ◽

Entry Inhibitors ◽

The Past ◽

Store Operated Calcium Entry

The store-operated calcium entry, better known as SOCE, forms the main Ca2+ influx pathway in non-excitable cells, especially in leukocytes, where it is required for cell activation and the immune response. During the past decades, several inhibitors were developed, but they lack specificity or efficacy. From the non-specific SOCE inhibitor 2-aminoethyl diphenylborinate (2-APB), we synthetized 16 new analogues by replacing/modifying the phenyl groups. Among them, our compound P11 showed the best inhibitory capacity with a Ki ≈ 75 nM. Furthermore, below 1 µM, P11 was devoid of any inhibitory activity on the two other main cellular targets of 2-APB, the IP3 receptors, and the SERCA pumps. Interestingly, Jurkat T cells secrete interleukin-2 under phytohemagglutinin stimulation but undergo cell death and stop IL-2 synthesis when stimulated in the presence of increasing P11 concentrations. Thus, P11 could represent the first member of a new and potent family of immunosuppressors.

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