Cell calcium最新文献

{"title":"Phosphorylation of phospholamban promotes SERCA2a activation by dwarf open reading frame (DWORF)","authors":"Elisa Bovo,&nbsp;Thomas Jamrozik,&nbsp;Daniel Kahn,&nbsp;Patryk Karkut,&nbsp;Seth L. Robia,&nbsp;Aleksey V. Zima","doi":"10.1016/j.ceca.2024.102910","DOIUrl":"10.1016/j.ceca.2024.102910","url":null,"abstract":"<div><p>In cardiac myocytes, the type 2a sarco/endoplasmic reticulum Ca<strong>-</strong>ATPase (SERCA2a) plays a key role in intracellular Ca regulation. Due to its critical role in heart function, SERCA2a activity is tightly regulated by different mechanisms, including micropeptides. While phospholamban (PLB) is a well-known SERCA2a inhibitor, dwarf open reading frame (DWORF) is a recently identified SERCA2a activator. Since PLB phosphorylation is the most recognized mechanism of SERCA2a activation during adrenergic stress, we studied whether PLB phosphorylation also affects SERCA2a regulation by DWORF. By using confocal Ca imaging in a HEK293 expressing cell system, we analyzed the effect of the co-expression of PLB and DWORF using a bicistronic construct on SERCA2a-mediated Ca uptake. Under these conditions of matched expression of PLB and DWORF, we found that SERCA2a inhibition by non-phosphorylated PLB prevails over DWORF activating effect. However, when PLB is phosphorylated at PKA and CaMKII sites, not only PLB's inhibitory effect was relieved, but SERCA2a was effectively activated by DWORF. Förster resonance energy transfer (FRET) analysis between SERCA2a and DWORF showed that DWORF has a higher relative affinity for SERCA2a when PLB is phosphorylated. Thus, SERCA2a regulation by DWORF responds to the PLB phosphorylation status, suggesting that DWORF might contribute to SERCA2a activation during conditions of adrenergic stress.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"121 ","pages":"Article 102910"},"PeriodicalIF":4.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141132256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Injection of luteinizing hormone or human chorionic gonadotropin increases calcium excretion and serum PTH in males","authors":"Li Juel Mortensen ,&nbsp;Ireen Kooij ,&nbsp;Mette Lorenzen ,&nbsp;Niklas Rye Jørgensen ,&nbsp;Andreas Røder ,&nbsp;Anne Jørgensen ,&nbsp;Anna-Maria Andersson ,&nbsp;Anders Juul ,&nbsp;Martin Blomberg Jensen","doi":"10.1016/j.ceca.2024.102908","DOIUrl":"10.1016/j.ceca.2024.102908","url":null,"abstract":"<div><p>Animal and human studies have suggested that sex steroids have calciotropic actions, and it has been proposed that follicle-stimulating hormone (FSH) may exert direct effects on bone. Here, we demonstrate the expression of the receptor for Luteinizing hormone (LH) and human choriogonadotropin (hCG), <em>LHCGR,</em> in human kidney tissue, suggesting a potential influence on calcium homeostasis. To investigate the role of LHCGR agonist on calcium homeostasis <em>in vivo</em>, we conducted studies in male mice and human subjects. Male mice were treated with luteinizing hormone (LH), and human extrapolation was achieved by injecting 5000 IU hCG once to healthy men or men with hypergonadotropic or hypogonadotropic hypogonadism. In mice, LH treatment significantly increased urinary calcium excretion and induced a secondary increase in serum parathyroid hormone (PTH). Similarly, hCG treatment in healthy men led to a significant increase in urinary calcium excretion, serum PTH levels, and 1,25 (OH)₂D₃, while calcitonin, and albumin levels were reduced, possibly to avoid development of persistent hypocalcemia. Still, the rapid initial decline in ionized calcium coincided with a significant prolongation of the cardiac QTc-interval that normalized over time. The observed effects may be attributed to LH/hCG-receptor (LHCGR) activation, considering the presence of LHCGR expression in human kidney tissue, and the increase in sex steroids occurred several hours after the changes in calcium homeostasis. Our translational study shed light on the intricate relationship between gonadotropins, sex hormones and calcium, suggesting that LHCGR may be influencing calcium homeostasis directly or indirectly.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"122 ","pages":"Article 102908"},"PeriodicalIF":4.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141131693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the complexity of the mitochondrial Ca2+ uniporter: regulation, tissue specificity, and physiological implications","authors":"Denis Vecellio Reane ,&nbsp;Julian D.C. Serna ,&nbsp;Anna Raffaello","doi":"10.1016/j.ceca.2024.102907","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102907","url":null,"abstract":"<div><p>Calcium (Ca²⁺) signalling acts a pleiotropic message within the cell that is decoded by the mitochondria through a sophisticated ion channel known as the Mitochondrial Ca²⁺ Uniporter (MCU) complex. Under physiological conditions, mitochondrial Ca²⁺ signalling is crucial for coordinating cell activation with energy production. Conversely, in pathological scenarios, it can determine the fine balance between cell survival and death. Over the last decade, significant progress has been made in understanding the molecular bases of mitochondrial Ca²⁺ signalling. This began with the elucidation of the MCU channel components and extended to the elucidation of the mechanisms that regulate its activity. Additionally, increasing evidence suggests molecular mechanisms allowing tissue-specific modulation of the MCU complex, tailoring channel activity to the specific needs of different tissues or cell types. This review aims to explore the latest evidence elucidating the regulation of the MCU complex, the molecular factors controlling the tissue-specific properties of the channel, and the physiological and pathological implications of mitochondrial Ca²⁺ signalling in different tissues.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"121 ","pages":"Article 102907"},"PeriodicalIF":4.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000654/pdfft?md5=8429ee5a865d1071486ceac007973991&pid=1-s2.0-S0143416024000654-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141084675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The A-kinase anchoring protein Yotiao decrease the ER calcium content by inhibiting the store operated calcium entry","authors":"Liuqing Wang ,&nbsp;Jiaxuan Zhang ,&nbsp;Wanjie Li ,&nbsp;Xiaoyan Zhang ,&nbsp;Tatsushi Yokoyama ,&nbsp;Masayuki Sakamoto ,&nbsp;Youjun Wang","doi":"10.1016/j.ceca.2024.102906","DOIUrl":"10.1016/j.ceca.2024.102906","url":null,"abstract":"<div><p>The meticulous regulation of ER calcium (Ca²⁺) homeostasis is indispensable for the proper functioning of numerous cellular processes. Disrupted ER Ca²⁺ balance is implicated in diverse diseases, underscoring the need for a systematic exploration of its regulatory factors in cells. Our recent genomic-scale screen identified a scaffolding protein A-kinase anchoring protein 9 (AKAP9) as a regulator of ER Ca²⁺ levels, but the underlying molecular mechanisms remain elusive. Here, we reveal that Yotiao, the smallest splicing variant of AKAP9 decreased ER Ca²⁺ content in animal cells. Additional testing using a combination of Yotiao truncations, knock-out cells and pharmacological tools revealed that, Yotiao does not require most of its interactors, including type 1 inositol 1,4,5-trisphosphate receptors (IP₃R1), protein kinase A (PKA), protein phosphatase 1 (PP1), adenylyl cyclase type 2 (AC2) and so on, to reduce ER Ca²⁺ levels. However, adenylyl cyclase type 9 (AC9), which is known to increases its cAMP generation upon interaction with Yotiao for the modulation of potassium channels, plays an essential role for Yotiao's ER-Ca²⁺-lowering effect. Mechanistically, Yotiao may work through AC9 to act on Orai1-C terminus and suppress store operated Ca²⁺ entry, resulting in reduced ER Ca²⁺ levels. These findings not only enhance our comprehension of the interplay between Yotiao and AC9 but also contribute to a more intricate understanding of the finely tuned mechanisms governing ER Ca²⁺ homeostasis.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"121 ","pages":"Article 102906"},"PeriodicalIF":4.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141039232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stretching the role of TMEM63a to gatekeeping Ca2+ release in pancreatic acinar cells","authors":"Sandip Patel ,&nbsp;David I. Yule","doi":"10.1016/j.ceca.2024.102890","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102890","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"121 ","pages":"Article 102890"},"PeriodicalIF":4.0,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140950372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anoctamin pharmacology","authors":"Michele Genovese ,&nbsp;Luis J.V. Galietta","doi":"10.1016/j.ceca.2024.102905","DOIUrl":"10.1016/j.ceca.2024.102905","url":null,"abstract":"<div><p>TMEM16 proteins, also known as anoctamins, are a family of ten membrane proteins with various tissue expression and subcellular localization. TMEM16A (anoctamin 1) is a plasma membrane protein that acts as a calcium-activated chloride channel. It is expressed in many types of epithelial cells, smooth muscle cells and some neurons. In airway epithelial cells, TMEM16A expression is particularly enhanced by inflammatory stimuli that also promote goblet cell metaplasia and mucus hypersecretion. Therefore, pharmacological modulation of TMEM16A could be beneficial to improve mucociliary clearance in chronic obstructive respiratory diseases. However, the correct approach to modulate TMEM16A activity (activation or inhibition) is still debated. Pharmacological inhibitors of TMEM16A could also be useful as anti-hypertensive agents given the TMEM16A role in smooth muscle contraction.</p><p>In contrast to TMEM16A, TMEM16F (anoctamin 6) behaves as a calcium-activated phospholipid scramblase, responsible for the externalization of phosphatidylserine on cell surface. Inhibitors of TMEM16F could be useful as anti-coagulants and anti-viral agents. The role of other anoctamins as therapeutic targets is still unclear since their physiological role is still to be defined.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"121 ","pages":"Article 102905"},"PeriodicalIF":4.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141044801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In or out of the groove? Mechanisms of lipid scrambling by TMEM16 proteins","authors":"Zhang Feng ,&nbsp;Eleonora Di Zanni ,&nbsp;Omar Alvarenga ,&nbsp;Sayan Chakraborty ,&nbsp;Nicole Rychlik ,&nbsp;Alessio Accardi","doi":"10.1016/j.ceca.2024.102896","DOIUrl":"10.1016/j.ceca.2024.102896","url":null,"abstract":"<div><p>Phospholipid scramblases mediate the rapid movement of lipids between membrane leaflets, a key step in establishing and maintaining membrane homeostasis of the membranes of all eukaryotic cells and their organelles. Thus, impairment of lipid scrambling can lead to a variety of pathologies. How scramblases catalyzed the transbilayer movement of lipids remains poorly understood. Despite the availability of direct structural information on three unrelated families of scramblases, the TMEM16s, the Xkrs, and ATG-9, a unifying mechanism has failed to emerge thus far. Among these, the most extensively studied and best understood are the Ca²⁺ activated TMEM16s, which comprise ion channels and/or scramblases. Early work supported the view that these proteins provided a hydrophilic, membrane-exposed groove through which the lipid headgroups could permeate. However, structural, and functional experiments have since challenged this mechanism, leading to the proposal that the TMEM16s distort and thin the membrane near the groove to facilitate lipid scrambling. Here, we review our understanding of the structural and mechanistic underpinnings of lipid scrambling by the TMEM16s and discuss how the different proposals account for the various experimental observations.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"121 ","pages":"Article 102896"},"PeriodicalIF":4.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140939304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the function and regulation of the calcium-activated chloride channel TMEM16A","authors":"Jorge Arreola ,&nbsp;Ana Elena López-Romero ,&nbsp;Miriam Huerta ,&nbsp;María Luisa Guzmán-Hernández ,&nbsp;Patricia Pérez-Cornejo","doi":"10.1016/j.ceca.2024.102891","DOIUrl":"10.1016/j.ceca.2024.102891","url":null,"abstract":"<div><p>The TMEM16A channel, a member of the TMEM16 protein family comprising chloride (Cl⁻) channels and lipid scramblases, is activated by the free intracellular Ca²⁺ increments produced by inositol 1,4,5-trisphosphate (IP3)-induced Ca²⁺ release after GqPCRs or Ca²⁺ entry through cationic channels. It is a ubiquitous transmembrane protein that participates in multiple physiological functions essential to mammals' lives. TMEM16A structure contains two identical 10-segment monomers joined at their transmembrane segment 10. Each monomer harbours one independent hourglass-shaped pore gated by Ca²⁺ ligation to an orthosteric site adjacent to the pore and controlled by two gates. The orthosteric site is created by assembling negatively charged glutamate side chains near the pore´s cytosolic end. When empty, this site generates an electrostatic barrier that controls channel rectification. In addition, an isoleucine-triad forms a hydrophobic gate at the boundary of the cytosolic vestibule and the inner side of the neck. When the cytosolic Ca²⁺ rises, one or two Ca²⁺ ions bind to the orthosteric site in a voltage (<em><strong>V</strong></em>)-dependent manner, thus neutralising the electrostatic barrier and triggering an allosteric gating mechanism propagating via transmembrane segment 6 to the hydrophobic gate. These coordinated events lead to pore opening, allowing the Cl⁻ flux to ensure the physiological response. The Ca²⁺-dependent function of TMEM16A is highly regulated. Anions with higher permeability than Cl⁻ facilitate <strong><em>V</em></strong> dependence by increasing the Ca²⁺ sensitivity, intracellular protons can replace Ca²⁺ and induce channel opening, and phosphatidylinositol 4,5-bisphosphate bound to four cytosolic sites likely maintains Ca²⁺ sensitivity. Additional regulation is afforded by cytosolic proteins, most likely by phosphorylation and protein-protein interaction mechanisms.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"121 ","pages":"Article 102891"},"PeriodicalIF":4.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141039496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WNK kinase, ion channels and arachidonic acid metabolites choreographically execute endothelium-dependent vasodilation","authors":"Jorge Arreola","doi":"10.1016/j.ceca.2024.102904","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102904","url":null,"abstract":"<div><p>The smooth muscle-walled blood vessels control blood pressure. The vessel lumen is lined by an endothelial cell (ECs) layer, interconnected to the surrounding smooth muscle cells (SMCs) by myoendothelial gap junctions. Gap junctions also maintain homo-cellular ECs-ECs and SMCs-SMCs connections. This gap junction network nearly equalises both cells' membrane potential and cytosolic ionic composition, whether in resting or stimulated conditions. When acetylcholine (ACh) activates ECs M3 receptors, a complex signalling cascade involving second messengers and ion channels is triggered to induce vasodilation.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"121 ","pages":"Article 102904"},"PeriodicalIF":4.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140894541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The dynamic TRPV2 ion channel proximity proteome reveals functional links of calcium flux with cellular adhesion factors NCAM and L1CAM in neurite outgrowth","authors":"Pamela N. Gallo ,&nbsp;Elaine Mihelc ,&nbsp;Robyn Eisert ,&nbsp;Gary A. Bradshaw ,&nbsp;Florian Dimek ,&nbsp;Andreas Leffler ,&nbsp;Marian Kalocsay ,&nbsp;Vera Moiseenkova-Bell","doi":"10.1016/j.ceca.2024.102894","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102894","url":null,"abstract":"<div><p>TRPV2 voltage-insensitive, calcium-permeable ion channels play important roles in cancer progression, immune response, and neuronal development. Despite TRPV2’s physiological impact, underlying endogenous proteins mediating TRPV2 responses and affected signaling pathways remain elusive. Using quantitative peroxidase-catalyzed (APEX2) proximity proteomics we uncover dynamic changes in the TRPV2-proximal proteome and identify calcium signaling and cell adhesion factors recruited to the molecular channel neighborhood in response to activation.</p><p>Quantitative TRPV2 proximity proteomics further revealed activation-induced enrichment of protein clusters with biological functions in neural and cellular projection. We demonstrate a functional connection between TRPV2 and the neural immunoglobulin cell adhesion molecules NCAM and L1CAM. NCAM and L1CAM stimulation robustly induces TRPV2 [Ca²⁺]_I flux in neuronal PC12 cells and this TRPV2-specific [Ca²⁺]_I flux requires activation of the protein kinase PKCα. TRPV2 expression directly impacts neurite lengths that are modulated by NCAM or L1CAM stimulation. Hence, TRPV2’s calcium signaling plays a previously undescribed, yet vital role in cell adhesion, and TRPV2 calcium flux and neurite development are intricately linked via NCAM and L1CAM cell adhesion proteins.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"121 ","pages":"Article 102894"},"PeriodicalIF":4.0,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140894542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}