Store-operated Ca2+ entry (SOCE) pathways

doi:10.1007/978-3-7091-0962-5

Cited by 4 publications

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References 652 publications

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“…SOCE is regulated by the calcium content at the lumen of the Endoplasmic Reticulum (ER). The release of calcium from the ER activates calcium influx from the extracellular space through store-operated channels (SOC) like Orai1 channels [1–8], and it involves the communication between two spatially independent membranes in the cell: the ER and plasma membrane (PM). The calcium depletion of the ER is sensed by the Stromal Interaction Molecule 1 (STIM1) [9,10], a multi-domain protein responsible of communicating the depleted state of the calcium repository (ER) to Orai1 channels [11,12], which are located at the PM.…”

Section: Introductionmentioning

confidence: 99%

Cholesterol modulates the cellular localization of Orai1 channels and its disposition among membrane domains

Bohórquez-Hernández

Gratton

Pacheco

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Store Operated Calcium Entry (SOCE) is one of the most important mechanisms for calcium mobilization in to the cell. Two main proteins sustain SOCE: STIM1 that acts as the calcium sensor in the endoplasmic reticulum (ER) and Orai1 responsible for calcium influx upon depletion of ER. There are many studies indicating that SOCE is modulated by the cholesterol content of the plasma membrane (PM). However, a myriad of questions remain unanswered concerning the precise molecular mechanism by which cholesterol modulates SOCE. In the present study we found that reducing PM cholesterol results in the internalization of Orai1 channels, which can be prevented by overexpressing caveolin 1 (Cav1). Furthermore, Cav1 and Orai1 associate upon SOCE activation as revealed by FRET and coimmunoprecipitation assays. The effects of reducing cholesterol were not limited to an increased rate of Orai1 internalization, but also, affects the lateral movement of Orai1, inducing movement in a linear pattern (unobstructed diffusion) opposite to basal cholesterol conditions were most of Orai1 channels moves in a confined space, as assessed by Fluorescence Correlation Spectroscopy, Cav1 overexpression inhibited these alterations maintaining Orai1 into a confined and partially confined movement. These results not only highlight the complex effect of cholesterol regulation on SOCE, but also indicate a direct regulatory effect on Orai1 localization and compartmentalization by this lipid.

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Section: Introductionmentioning

confidence: 99%

Cholesterol modulates the cellular localization of Orai1 channels and its disposition among membrane domains

Bohórquez-Hernández

Gratton

Pacheco

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Reorganization and suppression of store-operated calcium entry in podocytes induced by diabetes type 2

Gusev

Shalygin

Kolesnikov

et al. 2023

Preprint

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Type 2 diabetes mellitus (DM2) is a widespread metabolic disorder that results in podocyte damage and diabetic nephropathy. Previous studies demonstrated that TRPC6 channels play a pivotal role in podocyte function and their dysregulation is associated with development of different kidney diseases including nephropathy. It was assumed that activation of TRPC6 channels leads directly to the Ca2+ influx into cells. Another Ca2+ influx pathway, a store-operated Ca2+ entry (SOCE) via ORAI channels, was also shown to be disturbed during the diabetes development. Here, using single channel patch clamp technique, we demonstrated that non-selective cationic TRPC6 channels are sensitive to the Ca2+ store depletion in human podocyte cell line Ab8/13 and in freshly isolated rat glomerular podocytes. Ca2+ imaging indicated the involvement of ORAI and sodium-calcium exchanger (NCX) in Ca2+ entry induced upon store depletion. Ca2+ inflow by NCX is a result of pronounced TRPC6-mediated Na+ influx leading moreover to the membrane depolarization and ORAI suppression. In rats fed a high-fat diet combined with a low-dose streptozotocin injection, which leads to DM2 development, we observed the reduction of SOCE in rat glomerular podocytes. This was accompanied by a reorganization of store-operated Ca2+ influx such that TRPC6 channels lost their sensitivity to Ca2+ store depletion and ORAI-mediated Ca2+ entry is suppressed in TRPC6-independent manner. Altogether our data provide new insights into the mechanism of SOCE organization in podocytes in the norm and in pathology, which should be taken into account in the pharmacological treatment of the early stages of diabetic nephropathy.

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Reorganization and Suppression of Store-Operated Calcium Entry in Podocytes of Type 2 Diabetic Rats

Gusev

Shalygin

Kolesnikov

et al. 2023

IJMS

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Type 2 diabetes mellitus (DM2) is a widespread metabolic disorder that results in podocyte damage and diabetic nephropathy. Previous studies demonstrated that TRPC6 channels play a pivotal role in podocyte function and their dysregulation is associated with development of different kidney diseases including nephropathy. Here, using single channel patch clamp technique, we demonstrated that non-selective cationic TRPC6 channels are sensitive to the Ca2+ store depletion in human podocyte cell line Ab8/13 and in freshly isolated rat glomerular podocytes. Ca2+ imaging indicated the involvement of ORAI and sodium–calcium exchanger in Ca2+ entry induced upon store depletion. In male rats fed a high-fat diet combined with a low-dose streptozotocin injection, which leads to DM2 development, we observed the reduction of a store-operated Ca2+ entry (SOCE) in rat glomerular podocytes. This was accompanied by a reorganization of store-operated Ca2+ influx such that TRPC6 channels lost their sensitivity to Ca2+ store depletion and ORAI-mediated Ca2+ entry was suppressed in TRPC6-independent manner. Altogether our data provide new insights into the mechanism of SOCE organization in podocytes in the norm and in pathology, which should be taken into account when developing pharmacological treatment of the early stages of diabetic nephropathy.

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Store-operated Ca2+ entry (SOCE) pathways

Cited by 4 publications

References 652 publications

Cholesterol modulates the cellular localization of Orai1 channels and its disposition among membrane domains

Cholesterol modulates the cellular localization of Orai1 channels and its disposition among membrane domains

Reorganization and suppression of store-operated calcium entry in podocytes induced by diabetes type 2

Reorganization and Suppression of Store-Operated Calcium Entry in Podocytes of Type 2 Diabetic Rats

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