Calcium signalling articles within Nature Communications

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  • Article
    | Open Access

    The essential role of ORAI1 channels in receptor-evoked Ca2+ signaling is well understood, but the roles of ORAI2 and ORAI3 remained obscure. Here authors show that ORAI2 and ORAI3 channels multimerize with ORAI1 to expand the range of sensitivity of receptor-activated Ca2+ signals, reflecting their enhanced basal STIM1-binding and heightened Ca2+-dependent inactivation.

    • Ryan E. Yoast
    • , Scott M. Emrich
    •  & Mohamed Trebak

  • Article
    | Open Access

    The ability to manipulate and monitor calcium signaling in cells in vivo would provide insights into signaling in an endogenous context. Here the authors develop a two-photon-responsive calcium actuator and reporter combination to monitor the effect of calcium actuation on T cell migration, adhesion and chemokine release in vivo.

    • Armelle Bohineust
    • , Zacarias Garcia
    •  & Philippe Bousso

  • Article
    | Open Access

    Optogenetic tools have been used to control cellular behaviours but their use to probe structure-function relations of signalling proteins are underexplored. Here the authors engineer optogenetic modules into STIM1 to dissect molecular details of STIM1-mediated signalling and control various cellular events.

    • Guolin Ma
    • , Lian He
    •  & Yubin Zhou

  • Article
    | Open Access

    The extracellular cues regulating filamentous actin formation in somatic cell nuclei are unclear. Here, the authors show that activated GPCR signalling initiates transient accumulation of nuclear F-actin/formation in nuclear actin filaments, driven by calcium and requiring the nucleator Formin INF2.

    • Ying Wang
    • , Alice Sherrard
    •  & Robert Grosse

  • Article
    | Open Access

    Kidney stones form in the presence of overabundance of crystal-forming substances such as Ca2+ and oxalate. Here, the authors report genome-wide association analyses for kidney stone disease, report seven previously unknown loci and find that some of these loci also associate with Ca2+ concentration and excretion.

    • Sarah A. Howles
    • , Akira Wiberg
    •  & Dominic Furniss

  • Article
    | Open Access

    Dysregulation of intracellular calcium is reported in Alzheimer’s disease. Here the authors show that loss of the mitochondrial Na+ /Ca2+ exchanger, NCLX – primary route of mitochondrial calcium efflux, precedes neuronal pathology in experimental models and contributes to Alzheimer’s disease progression.

    • Pooja Jadiya
    • , Devin W. Kolmetzky
    •  & John W. Elrod

  • Article
    | Open Access

    Membrane contact sites between the ER and mitochondria are known to convey calcium signals between these two organelles via IP3 receptors, but the molecular mechanisms are currently unclear. Here, the authors show that IP3 receptors play a structural tethering role in maintaining ER-mitochondrial contacts.

    • Adam Bartok
    • , David Weaver
    •  & György Hajnóczky

  • Article
    | Open Access

    Proper mitochondrial structure is critical for normal function. Here, the authors show with SIM that the mitochondrial Ca2+ uniporter complex and localization of component MICU1 is critical to maintaining cristae junction stability and overall mitochondrial membrane structure.

    • Benjamin Gottschalk
    • , Christiane Klec
    •  & Wolfgang F. Graier

  • Article
    | Open Access

    Polycystin-2 (PC2) is an ion channel commonly found mutated in autosomal dominant polycystic kidney disease. Here Arhatte et al. identify transmembrane protein 33 (TMEM33) as a regulator of PC2 function at the endoplasmic reticulum, and find that deletion of TMEM33 protects mice from acute kidney injury.

    • Malika Arhatte
    • , Gihan S. Gunaratne
    •  & Amanda Patel

  • Article
    | Open Access

    ORAI1 constitutes the store-operated Ca2+ release-activated Ca2+ (CRAC) channel, but how this channel is turned off through Ca2+-dependent inactivation (CDI) remained unclear. Here the authors identify a spatially-restricted Ca2+/cAMP signaling crosstalk critical for mediating CDI which in turn regulates cellular Ca2+ signals and NFAT activation.

    • Xuexin Zhang
    • , Trayambak Pathak
    •  & Mohamed Trebak

  • Article
    | Open Access

    There are only few MRI-compatible calcium reporters and they are limited to measuring extracellular calcium levels. Here the authors develop and validate a cell-permeable, manganese-based paramagnetic MRI contrast agent that enables monitoring intracellular calcium signals in vivo in the rat brain.

    • Ali Barandov
    • , Benjamin B. Bartelle
    •  & Alan Jasanoff

  • Article
    | Open Access

    Calcium signalling downstream of VEGF is essential for VEGF-induced angiogenesis. Here Savage et al. show that Transmembrane Protein 33 (TMEM33) is required for angiogenesis and the endothelial calcium response to VEGF, revealing a function for TMEM33 in multicellular organisms.

    • Aaron M. Savage
    • , Sathishkumar Kurusamy
    •  & Robert N. Wilkinson

  • Article
    | Open Access

    Engagement of T cell receptors (TCRs) induces the formation of microclusters that mediate the downstream signalling events. Here the authors show, using high resolution TIRF-SIM and live cell imaging, that ZAP70 and LAT are recruited to TCR with distinct kinetics, with the delayed ZAP70-TCR association modulated by TCR-induced calcium flux.

    • Jason Yi
    • , Lakshmi Balagopalan
    •  & Lawrence E. Samelson

  • Article
    | Open Access

    The mechanisms that regulate the activity of Ca2 +/calmodulin-dependent protein kinase II (CaMKII) in the context of heart failure are incompletely understood. Here the authors show that protein arginine methyltransferase 1 (PRMT1) prevents cardiac hyperactivation of CaMKII and heart failure development by methylating CaMKII at arginine residues 9 and 275.

    • Jung-Hoon Pyun
    • , Hyun-Ji Kim
    •  & Jong-Sun Kang

  • Article
    | Open Access

    Stromal interaction molecule 1 (STIM1) monitors ER-luminal Ca2+ levels to maintain cellular Ca2+ balance. Here the authors find that the STIM1 luminal domain monomer has multiple Ca2+ - binding sites which set the threshold for physiological activation of STIM1 in cells.

    • Aparna Gudlur
    • , Ana Eliza Zeraik
    •  & Patrick G. Hogan

  • Article
    | Open Access

    Nitric oxide (NO) inhibits thrombosis in part by stimulating cyclic guanosine monophosphate (cGMP) production and cGMP-dependent protein kinase I (cGKI) activity in platelets. Here, Wen et al. develop a cGMP sensor mouse to follow cGMP dynamics in platelets, and find that shear stress activates NO-cGMP-cGKI signaling during platelet aggregation to limit thrombosis.

    • Lai Wen
    • , Susanne Feil
    •  & Robert Feil

  • Article
    | Open Access

    Genetic ablation of Mitochondrial Ca2+ uptake protein 1 (MICU1) in mouse induces higher rates of perinatal lethality. Here the authors show that MICU1 expression is regulated by hypoxia in a FOXD1-dependent manner, establishing a cyclic switch between glycolytic and oxidative metabolism during development.

    • Santhanam Shanmughapriya
    • , Dhanendra Tomar
    •  & Muniswamy Madesh

  • Article
    | Open Access

    G protein-coupled receptors (GPCRs) activate intracellular signalling pathways upon extracellular stimulation. Here authors record single cell responses of GPCR signalling which allows the direct estimation of its channel capacity for each cell along with the reproducibility of its response.

    • Amiran Keshelava
    • , Gonzalo P. Solis
    •  & Vladimir L. Katanaev

  • Article
    | Open Access

    Stormorken syndrome is associated with the R304W mutation in STIM1, which is a Calcium sensor in the endoplasmic reticulum. Here authors use FRET and electrophysiology to show that R304W induces STIM1 conformational extension by a dual mechanism resulting in constitutive activation of Ca2+ channels.

    • Marc Fahrner
    • , Michael Stadlbauer
    •  & Christoph Romanin

  • Article
    | Open Access

    Understanding the biological role of graphene in eukaryotic cells is essential for future biomedicine applications. Here, the authors investigate the interaction of neurons and fibroblasts with graphene substrates, which increase cell membrane cholesterol and potentiate neurotransmitter release and receptor signaling.

    • Kristina E. Kitko
    • , Tu Hong
    •  & Qi Zhang

  • Article
    | Open Access

    Calcium-independent phospholipase A2β (iPLA2β) is involved in many physiological and pathological processes but the underlying mechanisms are largely unknown. Here, the authors present the structure of dimeric iPLA2β, providing insights into the regulation of its activity and cellular localization.

    • Konstantin R. Malley
    • , Olga Koroleva
    •  & Sergey Korolev

  • Article
    | Open Access

    Insulin secretion by β-cells is stimulated by glucose and is dependent on the induction of β-cell membrane depolarization, mainly driven by the closure of KATP channels, which in turn promotes voltage-gated Ca2+ channel opening. Here Kang et al. show that the volume-regulated anion channel, SWELL1, is involved in glucose-stimulated calcium increase and insulin secretion.

    • Chen Kang
    • , Litao Xie
    •  & Rajan Sah

  • Article
    | Open Access

    STIM proteins sense Ca2+ depletion in the ER and activate store-operated Ca2+-entry (SOCE) in response, a process associated with dendritic cell functions. Here the authors show STIM1 is the major isoform controlling SOCE in mouse dendritic cells and provide a mechanism for its requirement in antigen cross-presentation.

    • Paula Nunes-Hasler
    • , Sophia Maschalidi
    •  & Nicolas Demaurex

  • Article
    | Open Access

    STIM proteins sense Ca2+ depletion in the ER and activate store-operated Ca2+ entry in response, a process associated with dendritic cell (DC) functions. Here, the authors show that optimal antigen cross-presentation in DCs requires the association of the chaperone molecule UNC93B1 with STIM1.

    • Sophia Maschalidi
    • , Paula Nunes-Hasler
    •  & Bénédicte Manoury

  • Article
    | Open Access

    The arterial wall is subjected to mechanical forces that modulate endothelial cell responses. Here, Mack and colleagues identify a novel role for Notch1 as a mechanosensor in adult arteries, where it ensures junctional integrity through modulation of calcium signalling and limits atherosclerosis.

    • Julia J. Mack
    • , Thiago S. Mosqueiro
    •  & M. Luisa Iruela-Arispe

  • Article
    | Open Access

    IP3 receptors mediate Ca2+ release from the endoplasmic reticulum. Here the authors show that only a small fraction of IP3 receptors initiate Ca2+ signals; these immobile IP3 receptors adjacent to the plasma membrane are optimally placed to control STIM1-dependent Ca2+ entry.

    • Nagendra Babu Thillaiappan
    • , Alap P. Chavda
    •  & Colin W. Taylor

  • Article
    | Open Access

    Store-operated calcium entry (SOCE) is elicited by the interaction of oligomerized STIM1 with plasma membrane Orai channels. Here, the authors show that this process is regulated by calmodulin, which binds STIM1 and disassembles the STIM1-Orai1 complex and STIM1 oligomers.

    • Xin Li
    • , Guangyan Wu
    •  & Yuequan Shen

  • Article
    | Open Access

    Bcl-2 interacting killer (Bik) decreases airway epithelial hyperplasia via apoptosis mediated by calcium release from the endoplasmic reticulum (ER), but the mechanism is unclear. Here the authors show that Bik promotes Bak enrichment at the ER to tether mitochondria for efficient calcium transfer.

    • Yohannes A. Mebratu
    • , Ivan Leyva-Baca
    •  & Yohannes Tesfaigzi

  • Article
    | Open Access

    In mammalian skeletal muscle, the DHPR functions as a voltage sensor to trigger muscle contraction and as a Ca2+ channel. Here the authors show that mice where Ca2+ influx through the DHPR is eliminated display no difference in skeletal muscle function, suggesting that the Ca2+ influx through this channel is vestigial.

    • Anamika Dayal
    • , Kai Schrötter
    •  & Manfred Grabner

  • Article
    | Open Access

    The mitochondrial uniporter MICU1 regulates mitochondrial Ca2+ uptake. Here, the authors show that MICU1 is upregulated in ovarian cancer and confers resistance to cisplatin-induced apoptosis through a Ca2+-mediated regulation of pyruvate dehydrogenase activity that results in increased glycolysis.

    • Prabir K. Chakraborty
    • , Soumyajit Banerjee Mustafi
    •  & Priyabrata Mukherjee

  • Article
    | Open Access

    Regulatory T cells (Tregs) promote immune suppression in the tumour. Here, the authors show that Tregs suppress cytotoxic T lymphocyte (CTL) activity by impairing Ca2+ signalling and that adoptive transfer of CTLs engineered with an optogenetic control of Ca2+overcome the immune suppression at the tumour site.

    • Kyun-Do Kim
    • , Seyeon Bae
    •  & Minsoo Kim

  • Article
    | Open Access

    Ca2+ release-activated Ca2+(CRAC) channels are essential for protective immunity, but the immunological functions of the three ORAI homologues that form CRAC channels are unclear. Here the authors show that ORAI1 and ORAI2 form heteromeric CRAC channels, which fine-tune T cell activation and immune responses.

    • Martin Vaeth
    • , Jun Yang
    •  & Stefan Feske

  • Article
    | Open Access

    How plasma membrane Orai Ca2+ channels are activated by STIM proteins to activate Ca2+signals is still not fully known. Here the authors show that a nexus region located at the Orai1 C-terminus allows channel gating without a direct interaction of STIM1 with the channel pore.

    • Yandong Zhou
    • , Xiangyu Cai
    •  & Donald L. Gill

  • Article
    | Open Access

    Characterization of T cell antigen specificity human blood is challenging due to the low clonal frequencies. Here the authors develop a fluorescent microscopy-based method to detect antigen-specific CD8 T cell activation, and apply it to characterize the anti-CMV repertoire.

    • Nadia Anikeeva
    • , Dolores Grosso
    •  & Yuri Sykulev

  • Article
    | Open Access

    The coupling of optogenetics with fluorescent Ca2+ sensors is confounded by sensitivity of optogenetic probes to light used to excite the sensors. Here the authors develop a Ca2+ sensor based on bioluminescence resonance energy transfer (BRET) that monitors Ca2+fluxes in darkness without excitation.

    • Jie Yang
    • , Derrick Cumberbatch
    •  & Carl Hirschie Johnson

  • Article
    | Open Access

    The binding of tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to nicotinic acetylcholine receptors (nAChRs) induces calcium signalling. Here the authors show that NKK-induced calcium influx in airway epithelial cells triggers IGF2 secretion and tumourigenesis.

    • Hye-Jin Boo
    • , Hye-Young Min
    •  & Ho-Young Lee

  • Article
    | Open Access

    MICU1 is a regulatory subunit of mitochondrial Ca2+ channels that shields mitochondria from Ca2+ overload. Here the authors show that MICU1 methylation by PRMT1 reduces Ca2+ sensitivity, which is normalized by UCP2/3, re-establishing mitochondrial Ca2+uptake activity.

    • Corina T. Madreiter-Sokolowski
    • , Christiane Klec
    •  & Wolfgang F. Graier

  • Article
    | Open Access

    Lymphocytic leukaemia cells are characterized by high respiratory rates. Here, the authors report that the oxysterol-binding protein ORPL4 sustains mitochondrial respiration in T-cell acute lymphoblastic leukaemia cells by regulating Ca2+release from the endoplasmic reticulum.

    • Wenbin Zhong
    • , Qing Yi
    •  & Daoguang Yan

  • Article
    | Open Access

    Two-photon laser scanning microscopy allows functional calcium imaging of large neuronal populations in vivo, but the recorded signals typically suffer from low signal to noise. Here the authors develop an algorithm, MLspike, which estimates action potentials from noisy calcium signals, and benchmark it against existing methods.

    • Thomas Deneux
    • , Attila Kaszas
    •  & Ivo Vanzetta

  • Article
    | Open Access

    Orai channels are well known to mediate store-operated calcium entry. Here authors show that in neurons of the Drosophilaflight circuit, Septin 7 acts as a negative regulator of Orai channels, surprisingly, by modulating store-independent calcium entry through Orai.

    • Bipan Kumar Deb
    • , Trayambak Pathak
    •  & Gaiti Hasan

  • Article
    | Open Access

    Heart failure is a major public health issue but due to our poor disease understanding the current therapies are symptomatic. Here the authors identify Myoscape as a novel cardiac protein regulating membrane localization of the L-type calcium channel and heart's contractile force, thus promising new therapeutic avenues for heart failure.

    • Matthias Eden
    • , Benjamin Meder
    •  & Norbert Frey

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