Cell calciumPub Date : 2024-07-27DOI: 10.1016/j.ceca.2024.102933
Julia Skerjanz , Lena Bauernhofer , Kerstin Lenk , Anita Emmerstorfer-Augustin , Gerd Leitinger , Florian Reichmann , Thomas Stockner , Klaus Groschner , Oleksandra Tiapko
{"title":"TRPC1: The housekeeper of the hippocampus","authors":"Julia Skerjanz , Lena Bauernhofer , Kerstin Lenk , Anita Emmerstorfer-Augustin , Gerd Leitinger , Florian Reichmann , Thomas Stockner , Klaus Groschner , Oleksandra Tiapko","doi":"10.1016/j.ceca.2024.102933","DOIUrl":"10.1016/j.ceca.2024.102933","url":null,"abstract":"<div><p>The non-selective cation channel TRPC1 is highly expressed in the brain. Recent research shows that neuronal TRPC1 forms heteromeric complexes with TRPC4 and TRPC5, with a small portion existing as homotetramers, primarily in the ER. Given that most studies have focused on the role of heteromeric TRPC1/4/5 complexes, it is crucial to investigate the specific role of homomeric TRPC1 in maintaining brain homeostasis. This review highlights recent findings on TRPC1 in the brain, with a focus on the hippocampus, and compiles the latest data on modulators and their binding sites within the TRPC1/4/5 subfamily to stimulate new research on more selective TRPC1 ligands.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"123 ","pages":"Article 102933"},"PeriodicalIF":4.3,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000915/pdfft?md5=a02753421b5354fe1513b6074ad37c26&pid=1-s2.0-S0143416024000915-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141843879","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}
Cell calciumPub Date : 2024-07-27DOI: 10.1016/j.ceca.2024.102932
Jinhyeong Kim , Kyu Pil Lee , Insuk So
{"title":"Periphery Pre-S1 and S1 helix nexus for PIP2 at TRPC3 channel","authors":"Jinhyeong Kim , Kyu Pil Lee , Insuk So","doi":"10.1016/j.ceca.2024.102932","DOIUrl":"10.1016/j.ceca.2024.102932","url":null,"abstract":"<div><p>Transient receptor potential canonical 3 (TRPC3) is a calcium-permeable, non-selective cation channel known to be regulated by components of the phospholipase C (PLC)-mediated signaling pathway, such as Ca<sup>2+</sup>, diacylglycerol (DAG) and phosphatidylinositol 4,5-biphosphate (PI(4,5)P<sub>2</sub>). However, the molecular gating mechanism by these regulators is not yet fully understood, especially its regulation by PI(4,5)P<sub>2</sub>, despite the importance of this channel in cardiovascular pathophysiology. Recently, Clarke et al. (2024) have reported that PI(4,5)P<sub>2</sub> is a positive modulator for TRPC3 using molecular dynamics simulations and patch-clamp techniques. They have demonstrated a multistep gating mechanism of TRPC3 with the binding of PI(4,5)P<sub>2</sub> to the lipid binding site located at the pre-S1/S1 nexus, and the propagation of PI(4,5)P<sub>2</sub> sensing to the pore domain via a salt bridge between the TRP helix and the S4–S5 linker.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"123 ","pages":"Article 102932"},"PeriodicalIF":4.3,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141849038","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}
Cell calciumPub Date : 2024-07-22DOI: 10.1016/j.ceca.2024.102931
Neha Gupta , Salah A. Baker , Kenton M. Sanders , Caoimhin S. Griffin , Gerard P. Sergeant , Mark A. Hollywood , Keith D. Thornbury , Bernard T. Drumm
{"title":"Interstitial cell of Cajal-like cells (ICC-LC) exhibit dynamic spontaneous activity but are not functionally innervated in mouse urethra","authors":"Neha Gupta , Salah A. Baker , Kenton M. Sanders , Caoimhin S. Griffin , Gerard P. Sergeant , Mark A. Hollywood , Keith D. Thornbury , Bernard T. Drumm","doi":"10.1016/j.ceca.2024.102931","DOIUrl":"10.1016/j.ceca.2024.102931","url":null,"abstract":"<div><p>Urethral smooth muscle cells (USMC) contract to occlude the internal urethral sphincter during bladder filling. Interstitial cells also exist in urethral smooth muscles and are hypothesized to influence USMC behaviours and neural responses. These cells are similar to Kit<sup>+</sup> interstitial cells of Cajal (ICC), which are gastrointestinal pacemakers and neuroeffectors. Isolated urethral ICC-like cells (ICC-LC) exhibit spontaneous intracellular Ca<sup>2+</sup> signalling behaviours that suggest these cells may serve as pacemakers or neuromodulators similar to ICC in the gut, although observation and direct stimulation of ICC-LC within intact urethral tissues is lacking. We used mice with cell-specific expression of the Ca<sup>2+</sup> indicator, GCaMP6f, driven off the endogenous promoter for <em>Kit</em> (Kit-GCaMP6f mice) to identify ICC-LC <em>in situ</em> within urethra muscles and to characterize spontaneous and nerve-evoked Ca<sup>2+</sup> signalling. ICC-LC generated Ca<sup>2+</sup> waves spontaneously that propagated on average 40.1 ± 0.7 μm, with varying amplitudes, durations, and spatial spread. These events originated from multiple firing sites in cells and the activity between sites was not coordinated. ICC-LC in urethra formed clusters but not interconnected networks. No evidence for entrainment of Ca<sup>2+</sup> signalling between ICC-LC was obtained. Ca<sup>2+</sup> events in ICC-LC were unaffected by nifedipine but were abolished by cyclopiazonic acid and decreased by an antagonist of Orai Ca<sup>2+</sup> channels (GSK-7975A). Phenylephrine increased Ca<sup>2+</sup> event frequency but a nitric oxide donor (DEA-NONOate) had no effect. Electrical field stimulation (EFS, 10 Hz) of intrinsic nerves, which evoked contractions of urethral rings and increased Ca<sup>2+</sup> event firing in USMC, failed to evoke responses in ICC-LC. Our data suggest that urethral ICC-LC are spontaneously active but are not regulated by autonomic neurons.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"123 ","pages":"Article 102931"},"PeriodicalIF":4.3,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000897/pdfft?md5=b7812ffdecf9e29cc0881b72c750836c&pid=1-s2.0-S0143416024000897-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141783399","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}
Cell calciumPub Date : 2024-07-20DOI: 10.1016/j.ceca.2024.102930
Donald M. Bers
{"title":"Cardiac Na-Ca exchanger “tunes-out” at high intracellular [Na]","authors":"Donald M. Bers","doi":"10.1016/j.ceca.2024.102930","DOIUrl":"10.1016/j.ceca.2024.102930","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"123 ","pages":"Article 102930"},"PeriodicalIF":4.3,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141783448","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}
Cell calciumPub Date : 2024-07-14DOI: 10.1016/j.ceca.2024.102929
Gaiti Hasan
{"title":"Septin regulation of Orai-mediated Ca2+ entry - a novel target for neurodegeneration","authors":"Gaiti Hasan","doi":"10.1016/j.ceca.2024.102929","DOIUrl":"10.1016/j.ceca.2024.102929","url":null,"abstract":"<div><p>Aberrant Ca<sup>2+</sup> signaling is an early hallmark of multiple neurodegenerative syndromes including Alzheimer's and Parkinson's disease (AD and PD) as well as classes of rare genetic disorders such as Spinocebellar Ataxias. Therapeutic strategies that target aberrant Ca<sup>2+</sup> signals whilst allowing normal neuronal Ca<sup>2+</sup> signals have been a challenge. In a recent study Princen et al., performed a screen in the tauP301L cell model of AD for drugs that could specifically ameliorate the excess Ca<sup>2+</sup> entry observed. They identified a class of compounds referred to as ReS19-T that interact with Septins, previously identified as regulators of the Store-operated Ca<sup>2+</sup> entry channel Orai. Drug treatment of the cellular model, a mouse model and human iPSC derived neurons alleviate cellular and systemic deficits associated with tauP301L. Comparison of Septin filament architecture in disease conditions with and without the drug treatment indicate that excess Ca<sup>2+</sup> entry is a consequence of abnormal Septin filament architecture resulting in aberrant ER-PM contacts. The importance of membrane contacts for maintaining precise cellular signaling has been recognized previously. However, the molecular mechanism by which Septin filaments organize the ER-PM junctions to regulate Ca<sup>2+</sup> entry through Orai remains to be fully understood.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"123 ","pages":"Article 102929"},"PeriodicalIF":4.3,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632763","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}
Cell calciumPub Date : 2024-07-06DOI: 10.1016/j.ceca.2024.102928
Myriam Torres-Rico , Virginia García-Calvo , Adrián Gironda-Martínez , Jorge Pascual-Guerra , Antonio G. García , Victoria Maneu
{"title":"Targeting calciumopathy for neuroprotection: focus on calcium channels Cav1, Orai1 and P2X7","authors":"Myriam Torres-Rico , Virginia García-Calvo , Adrián Gironda-Martínez , Jorge Pascual-Guerra , Antonio G. García , Victoria Maneu","doi":"10.1016/j.ceca.2024.102928","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102928","url":null,"abstract":"<div><p>As the uncontrolled entry of calcium ions (Ca<sup>2+</sup>) through plasmalemmal calcium channels is a cell death trigger, the conjecture is here raised that mitigating such an excess of Ca<sup>2+</sup> entry should rescue from death the vulnerable neurons in neurodegenerative diseases (NDDs). However, this supposition has failed in some clinical trials (CTs). Thus, a recent CT tested whether isradipine, a blocker of the Cav1 subtype of voltage-operated calcium channels (VOCCs), exerted a benefit in patients with Parkinson's disease (PD); however, outcomes were negative. This is one more of the hundreds of CTs done under the principle of one-drug-one-target, that have failed in Alzheimer's disease (AD) and other NDDs during the last three decades. As there are myriad calcium channels to let Ca<sup>2+</sup> ions gain the cell cytosol, it seems reasonable to predict that blockade of Ca<sup>2+</sup> entry through a single channel may not be capable of preventing the Ca<sup>2+</sup> flood of cells by the uncontrolled Ca<sup>2+</sup> entry. Furthermore, as Ca<sup>2+</sup> signaling is involved in the regulation of myriad functions in different cell types, it seems also reasonable to guess that a therapy should be more efficient by targeting different cells with various drugs. Here, we propose to mitigate Ca<sup>2+</sup> entry by the simultaneous partial blockade of three quite different subtypes of plasmalemmal calcium channels that is, the Cav1 subtype of VOCCs, the Orai1 store-operated calcium channel (SOCC), and the purinergic P2X7 calcium channel. All three channels are expressed in both microglia and neurons. Thus, by targeting the three channels with a combination of three drug blockers we expect favorable changes in some of the pathogenic features of NDDs, namely (i) to mitigate Ca<sup>2+</sup> entry into microglia; (ii) to decrease the Ca<sup>2+</sup>-dependent microglia activation; (iii) to decrease the sustained neuroinflammation; (iv) to decrease the uncontrolled Ca<sup>2+</sup> entry into neurons; (v) to rescue vulnerable neurons from death; and (vi) to delay disease progression. In this review we discuss the arguments underlying our triad hypothesis in the sense that the combination of three repositioned medicines targeting Cav1, Orai1, and P2X7 calcium channels could boost neuroprotection and delay the progression of AD and other NDDs.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"123 ","pages":"Article 102928"},"PeriodicalIF":4.3,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000861/pdfft?md5=11c1d21faaeacd324f82d6a1903836b4&pid=1-s2.0-S0143416024000861-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141607645","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}
Cell calciumPub Date : 2024-06-28DOI: 10.1016/j.ceca.2024.102927
Brett Boonen, Thomas Voets
{"title":"A frozen portrait of a warm channel","authors":"Brett Boonen, Thomas Voets","doi":"10.1016/j.ceca.2024.102927","DOIUrl":"10.1016/j.ceca.2024.102927","url":null,"abstract":"<div><p>In order to understand protein function, the field of structural biology makes extensive use of cryogenic electron microscopy (cryo-EM), a technique that enables structure determination at atomic resolution following embedding of protein particles in vitreous ice. Considering the profound effects of temperature on macromolecule function, an important—but often neglected-question is how the frozen particles relate to the actual protein conformations at physiological temperatures. In a recent study, Hu et al. compare structures of the cation channel TRPM4 “frozen” at 4 °C versus 37 °C, revealing how temperature critically affects the binding of activating Ca<sup>2+</sup> ions and other channel modulators.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"123 ","pages":"Article 102927"},"PeriodicalIF":4.3,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497161","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}
Cell calciumPub Date : 2024-06-24DOI: 10.1016/j.ceca.2024.102926
Emanuela Pessolano , Zlata A. Sosic , Armando A. Genazzani
{"title":"STIM1: A new player in nuclear dynamics? Lessons learnt from tubular aggregate myopathy","authors":"Emanuela Pessolano , Zlata A. Sosic , Armando A. Genazzani","doi":"10.1016/j.ceca.2024.102926","DOIUrl":"10.1016/j.ceca.2024.102926","url":null,"abstract":"<div><p>Two recent papers have highlighted that STIM1, a key component of Store-operated Ca2+-entry, is able to translocate to the nucleus and participate in nuclear Ca<sup>2+</sup>-handling and in DNA repair. These finding opens new avenues on the role that this Ca<sup>2+</sup>-sensing protein may have in health and disease.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"123 ","pages":"Article 102926"},"PeriodicalIF":4.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497162","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}