Cell calcium最新文献

{"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}

{"title":"Calreticulin regulates hepatic stellate cell activation through modulating TGF-beta-induced Smad signaling","authors":"Chien-Chih Chen ,&nbsp;Li-Wen Hsu ,&nbsp;Kuang-Den Chen ,&nbsp;King-Wah Chiu ,&nbsp;Chao-Pin Kung ,&nbsp;Shu-Rong Li ,&nbsp;Chao-Long Chen ,&nbsp;Kuang-Tzu Huang","doi":"10.1016/j.ceca.2024.102895","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102895","url":null,"abstract":"<div><p>Liver fibrosis is characterized by excessive deposition of extracellular matrix (ECM) as a wound healing process. Activated hepatic stellate cells (HpSCs) are the major producer of the ECM and play a central role in liver fibrogenesis. It has been widely accepted that elimination of activated HpSCs or reversion to a quiescent state can be a feasible strategy for resolving the disease, further highlighting the urgent need for novel therapeutic targets. Calreticulin (CRT) is a molecular chaperone that normally resides in the endoplasmic reticulum (ER), important in protein folding and trafficking through the secretory pathway. CRT also plays a critical role in calcium (Ca²⁺) homeostasis, with its Ca²⁺ storage capacity. In the current study, we aimed to demonstrate its function in directing HpSC activation. In a mouse liver injury model, CRT was up-regulated in HpSCs. In cellular experiments, we further showed that this activation was through modulating the canonical TGF-β signaling. As down-regulation of CRT in HpSCs elevated intracellular Ca²⁺ levels through a form of Ca²⁺ influx, named store-operated Ca²⁺ entry (SOCE), we examined whether moderating SOCE affected TGF-β signaling. Interestingly, blocking SOCE had little effect on TGF-β-induced gene expression. In contrast, inhibition of ER Ca²⁺ release using the inositol trisphosphate receptor inhibitor 2-APB increased TGF-β signaling. Treatment with 2-APB did not alter SOCE but decreased intracellular Ca²⁺ at the basal level. Indeed, adjusting Ca²⁺ concentrations by EGTA or BAPTA-AM chelation further enhanced TGF-β-induced signaling. Our results suggest a crucial role of CRT in the liver fibrogenic process through modulating Ca²⁺ concentrations and TGF-β signaling in HpSCs, which may provide new information and help advance the current discoveries for liver fibrosis.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"121 ","pages":"Article 102895"},"PeriodicalIF":4.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140824431","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":"Orai1/STIMs modulators in pulmonary vascular diseases","authors":"Anaïs Saint-Martin Willer ,&nbsp;David Montani ,&nbsp;Véronique Capuano ,&nbsp;Fabrice Antigny","doi":"10.1016/j.ceca.2024.102892","DOIUrl":"10.1016/j.ceca.2024.102892","url":null,"abstract":"<div><p>Calcium (Ca²⁺) is a secondary messenger that regulates various cellular processes. However, Ca²⁺ mishandling could lead to pathological conditions. Orai1 is a Ca²⁺channel contributing to the store-operated calcium entry (SOCE) and plays a critical role in Ca²⁺ homeostasis in several cell types. Dysregulation of Orai1 contributed to severe combined immune deficiency syndrome, some cancers, pulmonary arterial hypertension (PAH), and other cardiorespiratory diseases. During its activation process, Orai1 is mainly regulated by stromal interacting molecule (STIM) proteins, especially STIM1; however, many other regulatory partners have also been recently described. Increasing knowledge about these regulatory partners provides a better view of the downstream signalling pathways of SOCE and offers an excellent opportunity to decipher Orai1 dysregulation in these diseases. These proteins participate in other cellular functions, making them attractive therapeutic targets. This review mainly focuses on Orai1 regulatory partners in the physiological and pathological conditions of the pulmonary circulation and inflammation.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"121 ","pages":"Article 102892"},"PeriodicalIF":4.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000502/pdfft?md5=aaccf561946fb9b4e10e4964cedbd2af&pid=1-s2.0-S0143416024000502-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140760190","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":"A deep learning-based approach for efficient detection and classification of local Ca²⁺ release events in Full-Frame confocal imaging","authors":"Prisca Dotti ,&nbsp;Miguel Fernandez-Tenorio ,&nbsp;Radoslav Janicek ,&nbsp;Pablo Márquez-Neila ,&nbsp;Marcel Wullschleger ,&nbsp;Raphael Sznitman ,&nbsp;Marcel Egger","doi":"10.1016/j.ceca.2024.102893","DOIUrl":"10.1016/j.ceca.2024.102893","url":null,"abstract":"<div><p>The release of Ca²⁺ ions from intracellular stores plays a crucial role in many cellular processes, acting as a secondary messenger in various cell types, including cardiomyocytes, smooth muscle cells, hepatocytes, and many others. Detecting and classifying associated local Ca²⁺ release events is particularly important, as these events provide insight into the mechanisms, interplay, and interdependencies of local Ca²⁺release events underlying global intracellular Ca²⁺signaling. However, time-consuming and labor-intensive procedures often complicate analysis, especially with low signal-to-noise ratio imaging data.</p><p>Here, we present an innovative deep learning-based approach for automatically detecting and classifying local Ca²⁺ release events. This approach is exemplified with rapid full-frame confocal imaging data recorded in isolated cardiomyocytes.</p><p>To demonstrate the robustness and accuracy of our method, we first use conventional evaluation methods by comparing the intersection between manual annotations and the segmentation of Ca²⁺ release events provided by the deep learning method, as well as the annotated and recognized instances of individual events. In addition to these methods, we compare the performance of the proposed model with the annotation of six experts in the field. Our model can recognize more than 75 % of the annotated Ca²⁺ release events and correctly classify more than 75 %. A key result was that there were no significant differences between the annotations produced by human experts and the result of the proposed deep learning model.</p><p>We conclude that the proposed approach is a robust and time-saving alternative to conventional full-frame confocal imaging analysis of local intracellular Ca²⁺ events.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"121 ","pages":"Article 102893"},"PeriodicalIF":4.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000514/pdfft?md5=65d9d2a8d9dd3099c371aa508ba13fc9&pid=1-s2.0-S0143416024000514-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140776277","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 tether function of the anoctamins","authors":"Wei-Yin Lin,&nbsp;Woo Young Chung,&nbsp;Shmuel Muallem","doi":"10.1016/j.ceca.2024.102875","DOIUrl":"10.1016/j.ceca.2024.102875","url":null,"abstract":"<div><p>The core functions of the anoctamins are Cl⁻ channel activity and phosphatidylserine (and perhaps other lipids) scrambling. These functions have been extensively studied in various tissues and cells. However, another function of the anoctamins that is less recognized and minimally explored is as tethers at membrane contact sites. This short review aims to examine evidence supporting the localization of the anoctamins at membrane contact sites, their tether properties, and their functions as tethers.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"121 ","pages":"Article 102875"},"PeriodicalIF":4.0,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140779286","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 physiological roles of anoctamin2/TMEM16B and anoctamin1/TMEM16A in chemical senses","authors":"Michele Dibattista ,&nbsp;Simone Pifferi ,&nbsp;Andres Hernandez-Clavijo ,&nbsp;Anna Menini","doi":"10.1016/j.ceca.2024.102889","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102889","url":null,"abstract":"<div><p>Chemical senses allow animals to detect and discriminate a vast array of molecules. The olfactory system is responsible of the detection of small volatile molecules, while water dissolved molecules are detected by taste buds in the oral cavity. Moreover, many animals respond to signaling molecules such as pheromones and other semiochemicals through the vomeronasal organ. The peripheral organs dedicated to chemical detection convert chemical signals into perceivable information through the employment of diverse receptor types and the activation of multiple ion channels. Two ion channels, TMEM16B, also known as anoctamin2 (ANO2) and TMEM16A, or anoctamin1 (ANO1), encoding for Ca²⁺-activated Cl¯ channels, have been recently described playing critical roles in various cell types. This review aims to discuss the main properties of TMEM16A and TMEM16B-mediated currents and their physiological roles in chemical senses. In olfactory sensory neurons, TMEM16B contributes to amplify the odorant response, to modulate firing, response kinetics and adaptation. TMEM16A and TMEM16B shape the pattern of action potentials in vomeronasal sensory neurons increasing the interspike interval. In type I taste bud cells, TMEM16A is activated during paracrine signaling mediated by ATP. This review aims to shed light on the regulation of diverse signaling mechanisms and neuronal excitability mediated by Ca-activated Cl¯ channels, hinting at potential new roles for TMEM16A and TMEM16B in the chemical senses.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"120 ","pages":"Article 102889"},"PeriodicalIF":4.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140649837","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":"VSI: The anoctamins: Structure and function","authors":"Karl Kunzelmann,&nbsp;Jiraporn Ousingsawat,&nbsp;Rainer Schreiber","doi":"10.1016/j.ceca.2024.102888","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102888","url":null,"abstract":"<div><p>Plasma membrane localized anoctamin 1, 2 and 6 (TMEM16A, B, F) have been examined in great detail with respect to structure and function, but much less is known about the other seven intracellular members of this exciting family of proteins. This is probably due to their limited accessibility in intracellular membranous compartments, such as the endoplasmic reticulum (ER) or endosomes. However, these so-called intracellular anoctamins are also found in the plasma membrane (PM) which adds to the confusion regarding their cellular role. Probably all intracellular anoctamins except of ANO8 operate as intracellular phospholipid (PL) scramblases, allowing for Ca²⁺-activated, passive transport of phospholipids like phosphatidylserine between both membrane leaflets. Probably all of them also conduct ions, which is probably part of their physiological function. In this brief overview, we summarize key findings on the biological functions of ANO3, 4, 5, 7, 8, 9 and 10 (TMEM16C, D, E, G, H, J, K) that are gradually coming to light. Compartmentalized regulation of intracellular Ca²⁺ signals, tethering of the ER to specific PM contact sites, and control of intracellular vesicular trafficking appear to be some of the functions of intracellular anoctamins, while loss of function and abnormal expression are the cause for various diseases.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"120 ","pages":"Article 102888"},"PeriodicalIF":4.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000460/pdfft?md5=f58aed71b2a266518534bd100bcaf091&pid=1-s2.0-S0143416024000460-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140640944","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}