Article
Neurosciences
Alexandre Bouron
Summary: The endoplasmic reticulum (ER) is the primary storage compartment for calcium (Ca2+) in eukaryotic cells. Ca2+ is mobilized from the ER through store-operated Ca2+ channels (SOCCs), leading to a store-operated Ca2+ entry (SOCE) that has been extensively studied in non-excitable cells. The presence of this Ca2+ entry route in neurons has been a subject of debate, but experimental evidence suggests that SOCE can be generated by the recruitment of Ca2+ from neuronal ER Ca2+ stores. This review summarizes the main supporting studies and explores the molecular composition, expression, pharmacological properties, and physiological relevance of neuronal SOCCs.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Daniel Bakowski, Fraser Murray, Anant B. Parekh
Summary: CRAC channels are a major route for calcium entry in eukaryotic cells and have important implications in human diseases. Recent advances in understanding their structure have led to potential clinical applications, with CRAC channel blockers now entering clinical trials.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021
(2021)
Review
Cell Biology
Elena Lilliu, Stephane Koenig, Xaver Koenig, Maud Frieden
Summary: This study focuses on the peculiar aspects of skeletal muscle SOCE, differentiating it from its counterpart in non-excitable cells. It explores issues such as SOCE localization, protein movement, diversity of STIM isoforms, and the activation of phasic SOCE during EC coupling. The complexity of SOCE activation and regulation in skeletal muscle is highlighted, with an emphasis on the most recent findings.
Review
Physiology
Declan Manning, Caroline Dart, Richard L. Evans
Summary: The skin is a complex organ with various functions such as protection, temperature regulation, sensation, immune surveillance, and biochemical functions. Dysfunction in store-operated channels is linked to skin pathologies, and these channels play vital roles in the normal physiology and function of the skin.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yihan Shen, Nagendra Babu Thillaiappan, Colin W. Taylor
Summary: Increases in cytosolic Ca2+ concentration regulate cellular activities mainly through STIM1 and Orai1 mediated Ca2+ release and channel opening. Each native SOCE complex likely consists of only a few STIM1 dimers associated with a single Orai1 channel.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Bastien Masson, David Montani, Marc Humbert, Veronique Capuano, Fabrice Antigny
Summary: Pulmonary arterial hypertension (PAH) is a severe and multifactorial disease mostly involving dysfunction of pulmonary arterial endothelial and smooth muscle cells. Current therapies target endothelial dysfunction, while smooth muscle cell dysfunction is under investigation. Modifications in intracellular Ca2+ homeostasis, particularly through store-operated Ca2+ channels, may play a role in PAH pathogenesis and potential therapeutic interventions.
Article
Oncology
Jiazhang Wei, Yayan Deng, Jiaxiang Ye, Yue Luo, Jingjin Weng, Qian He, Fei Liu, Min Li, Rong Liang, Yan Lin, Yongqiang Li, Jinyan Zhang, Jianrong Yang, Shenhong Qu
Summary: Recent studies have shown that alterations in SOCE play a critical role in tumor metastasis, with dysregulated expression of STIM/ORAI potentially serving as an indicator of poor prognosis. SOCE contributes significantly to EMT, tumor cell migration and invasion, and angiogenesis, suggesting it could be a feasible target for cancer treatment.
Article
Oncology
Elodie Terrie, Nadine Deliot, Yassine Benzidane, Thomas Harnois, Laetitia Cousin, Patrick Bois, Lisa Oliver, Patricia Arnault, Francois Vallette, Bruno Constantin, Valerie Coronas
Summary: The calcium pathways in glioblastoma stem cells have been highlighted, with pharmacological inhibition of store-operated channels shown to significantly reduce cell proliferation and stem cell self-renewal. These findings contribute to the identification of potential new therapies against glioblastoma.
Article
Geriatrics & Gerontology
Nawfel Mokrane, Yassin Snabi, Thierry Cens, Janique Guiramand, Pierre Charnet, Anais Bertaud, Claudine Menard, Matthieu Rousset, Marie-Celeste de Jesus Ferreira, Jean-Baptiste Thibaud, Catherine Cohen-Solal, Michel Vignes, Julien Roussel
Summary: Changes in the redox status of astrocytes can significantly modify Ca2+ responses, impacting cellular excitability under purinergic stimulation. This could play a crucial role in understanding neuronal damage caused by oxidative stress.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Cell Biology
Julia Hermes, Vesela Borisova, Jens Kockskaemper
Summary: This study investigates the mechanisms of store-operated calcium entry (SOCE) in cardiomyocytes and its potential role in cardiac remodeling. The results show that SOCE can increase nuclear calcium levels and alter gene expression through calcium/calmodulin-dependent enzyme signaling. Both TRPC and Orai channels may contribute to SOCE in adult cardiomyocytes, with larger SOCE amplitudes observed in atrial myocytes compared to ventricular myocytes.
Article
Physiology
Declan Manning, Richard Barrett-Jolley, Richard L. Evans, Caroline Dart
Summary: Skin is the largest organ in the human body, mainly composed of keratinocytes which maintain a healthy skin barrier through regulated differentiation driven by Ca2+-transcriptional coupling. Disruption of this process leads to various skin conditions. Our study suggests that TRPC2 and Orai1 channels do not insert into the plasma membrane during store-operated Ca2+ entry.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Konstantin Gusev, Alexey Shalygin, Dmitrii Kolesnikov, Leonid Shuyskiy, Sofia Makeenok, Lyubov Glushankova, Konstantin Sivak, Kirill Yakovlev, Yana Orshanskaya, Guanghui Wang, Andrey Bakhtyukov, Kira Derkach, Alexander Shpakov, Elena Kaznacheyeva
Summary: Research shows that TRPC6 channels play a crucial role in podocyte function and their dysregulation is associated with kidney diseases. Through single channel patch clamp technique, it is found that TRPC6 channels in human podocytes and rat glomerular podocytes are sensitive to calcium store depletion. In a rat model of DM2, a reduction in store-operated calcium entry was observed in glomerular podocytes, along with a reorganization of calcium influx mediated by TRPC6 channels and ORAI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Yan Chang, Souvik Roy, Zui Pan
Summary: The review discusses the impact of dysregulated store-operated calcium entry (SOCE) on gastroesophageal cancers, including its role in cancer cell proliferation, migration, invasion, and stemness maintenance. Efforts towards developing more specific and potent SOCE inhibitors as a new set of chemotherapeutic drugs for targeted therapy or adjuvant treatment to overcome drug resistance in gastroesophageal cancers are also highlighted.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Chemistry, Medicinal
Hussein N. N. Rubaiy
Summary: Changes in intracellular calcium levels play a crucial role in regulating cell function and are linked to various human diseases. Store-operated calcium entry mediated by Orai and STIM channels is involved in important cell signaling processes and has been identified as a potential drug target. This review summarizes our current knowledge of the role of Orai/STIM channels in diseases such as immunodeficiency, myopathy, and cancer, and suggests their therapeutic potential. Additionally, the review focuses on pharmacological modulators of Orai/STIM channels and highlights the need for identifying small molecules for therapeutic intervention.
Editorial Material
Cell Biology
Alexandre Bouron
Summary: This article reveals the molecular mechanism of ER Ca2+ depletion activating store-operated Ca2+ entry, and discovers a new type of coupling distinct from Orai, expanding the understanding of store-operated ion channel signaling.
Article
Biochemistry & Molecular Biology
Francisco Sadras, Teneale A. Stewart, Melanie Robitaille, Amelia A. Peters, Priyakshi Kalita-de Croft, Patsy S. Soon, Jodi M. Saunus, Sunil R. Lakhani, Sarah J. Roberts-Thomson, Gregory R. Monteith
Summary: The role of calcium signalling pathways in inducing CAF phenotype has not been fully explored. A CAF model was generated by stimulating normal human mammary fibroblast cells with TGF beta 1, leading to altered calcium influx pathways. Upregulation of VGCCs Ca(V)1.2 and Ca(V)3.2 was observed in both the model and patient-derived breast CAFs, and inhibiting these channels impaired CAF activation. Targeting calcium signalling in breast CAFs could have a therapeutic potential.
Article
Biochemistry & Molecular Biology
John J. Bassett, Melanie Robitaille, Amelia A. Peters, Alice H. L. Bong, Meng-Wong Taing, Ian A. Wood, Francisco Sadras, Sarah J. Roberts-Thomson, Gregory R. Monteith
Summary: Excessive rapid increases in cytosolic free Ca2+ are associated with cancer cell death. In this study, it was found that staurosporine-induced apoptosis in breast cancer cells led to delayed cytosolic free Ca2+ fluctuations, which persisted for 24 hours. These fluctuations depended on the Ca2+ channel ORAI1, and silencing ORAI1 promoted apoptosis.
Review
Biochemistry & Molecular Biology
Francisco Sadras, Gregory R. Monteith, Sarah J. Roberts-Thomson
Summary: Tumors interact with their microenvironment, particularly with cancer-associated fibroblasts (CAFs), which play a significant role in supporting cancer development through various processes like cell-cell contact, paracrine signaling, and extracellular matrix remodeling. Calcium signaling, a key player in intra- and intercellular pathways, is less explored in connection with CAFs, but it contributes to cancer progression, especially in processes like migration, proliferation, chemoresistance, and genetic instability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Choon Leng So, Christoph Meinert, Qing Xia, Melanie Robitaille, Sarah J. Roberts-Thomson, Gregory R. Monteith
Summary: Both matrix stiffness and remodeling of calcium signaling are associated with the progression of breast cancers. This study assessed calcium signaling in breast cancer cells at different matrix stiffness using gel culture models and MDA-MB-231 cells expressing the calcium sensor GCaMP6m. The results showed that higher matrix stiffness attenuates ATP-induced sustained calcium influx in breast cancer cells.
Editorial Material
Cell Biology
Gregory R. Monteith, Melanie Robitaille, Sarah J. Roberts-Thomson
Article
Biochemistry & Molecular Biology
Melanie Robitaille, Shao Ming Chan, Amelia A. Peters, Limin Dai, Choon Leng So, Alice H. L. Bong, Francisco Sadras, Sarah J. Roberts-Thomson, Gregory R. Monteith
Summary: Remodeling of calcium homeostasis, including SOCE, plays a crucial role in breast cancer. ORAI1, a key regulator of SOCE, is upregulated in basal breast cancer cells. The study reveals that ORAI1 is involved in the regulation of gene transcription in basal breast cancer cells and may contribute to cancer progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Alice Hui Li Bong, Trinh Hua, Choon Leng So, Amelia A. Peters, Melanie Robitaille, Yin Yi Tan, Sarah J. Roberts-Thomson, Gregory R. Monteith
Summary: The interplay between calcium homeostasis and the AKT signaling pathway in breast cancer cells remains unclear, but it may provide potential therapeutic targets. This study highlights a novel correlation between AKT activation and increased calcium entry mediated by ORAI1 calcium channels. Targeting ORAI1 may be a promising therapeutic strategy for breast cancers with abnormal AKT signaling.
Editorial Material
Cell Biology
Choon Leng So, Melanie Robitaille, Gregory R. Monteith
Article
Cell Biology
Ellen K. Janke, Silke B. Chalmers, Sarah J. Roberts-Thomson, Gregory R. Monteith
Summary: Epithelial-mesenchymal transition (EMT) is a critical step in cancer progression and is associated with the remodeling of calcium (Ca2+) signaling pathways. This review explores the complex interplay between Ca2+ signaling and EMT, highlighting the potential therapeutic opportunities in regulating EMT through Ca2+ signaling. However, the complexity of these pathways presents challenges in manipulating Ca2+ signaling for therapeutic intervention in cancer.
