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| Open AccessCalcium-sensing receptors signal constitutive macropinocytosis and facilitate the uptake of NOD2 ligands in macrophages
Macropinocytosis can be induced in several cell types by growth factors to promote nutrient acquisition. Here the authors find that constitutive macropinocytosis, unique to dendritic cells and macrophages, requires the activity of calcium-sensing receptors.
- Johnathan Canton
- , Daniel Schlam
- & Sergio Grinstein
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| Open AccessCalcium imaging reveals glial involvement in transcranial direct current stimulation-induced plasticity in mouse brain
While transcranical direct current stimulation (tDCS) is used in clinical setting, its cellular mechanism of action is unclear. Here, Hajime Hirase and colleagues visualize cellular response in mouse brain to tDCS and show robust astrocyte activation that coincide with plasticity changes.
- Hiromu Monai
- , Masamichi Ohkura
- & Hajime Hirase
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| Open AccessMICU1 regulation of mitochondrial Ca2+ uptake dictates survival and tissue regeneration
Mitochondrial calcium uptake is a highly regulated process, and calcium overload can lead to cell death. Here, using knockout mouse model, the authors show that the mitochondrial calcium uniporter (MCU) regulator MICU1 is needed to prevent calcium overload and promotes survival under liver regeneration and postnatal adaptation-associated stress.
- Anil Noronha Antony
- , Melanie Paillard
- & György Hajnóczky
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| Open AccessImpairment of PARK14-dependent Ca2+ signalling is a novel determinant of Parkinson’s disease
PLA2g6 regulates store-operated Ca2+ entry and is linked to Parkinson’s disease. Here, Zhou et al find faulty PLA2g6-dependent Ca2+signaling in idiopathic PD patients, and show that its impairment triggers autophagic dysfunction and loss of dopaminergic neurons in a new PLA2g6 ex2KO mouse model.
- Qingde Zhou
- , Allen Yen
- & Victoria M. Bolotina
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| Open AccessCalcium ions open a selectivity filter gate during activation of the MthK potassium channel
Ion channels open and close to allow the regulated passage of ions through the membrane. Here the authors use selective ion channel blockers to analyse this regulation in a potassium channel and show that the gate is in the selectivity filter, past the entrance to the channel.
- David J. Posson
- , Radda Rusinova
- & Crina M. Nimigean
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| Open AccessLight generation of intracellular Ca2+ signals by a genetically encoded protein BACCS
Current tools for optogenetic control of intracellular calcium signals currently suffer from slow response time or low dynamic range. Here the authors develop blue light-activated Ca2+ channel switch (BACCS) that modulates the activity of Ca2+-sensitive Orai channels with high temporal resolution and large dynamic range.
- Tomohiro Ishii
- , Koji Sato
- & Takao Nakata
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Article
| Open AccessCrystal structures of ryanodine receptor SPRY1 and tandem-repeat domains reveal a critical FKBP12 binding determinant
The ryanodine receptor (RyR) is a large multi-domain ion channel that functions to release calcium from the endoplasmic or sarcoplasmic reticulum. Here the authors present crystal structures of the SPRY1 and tandem repeat domains of RyR, allowing precise positioning of the domains and linking disease mutations to RyR function.
- Zhiguang Yuchi
- , Siobhan M. Wong King Yuen
- & Filip Van Petegem
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| Open AccessNonsynaptic junctions on myelinating glia promote preferential myelination of electrically active axons
The myelin sheath on vertebrate axons is critical for neural impulse transmission, but whether electrically active axons are preferentially myelinated by glial cells, is not clear. Here the authors show that cultured oligodendrocytes preferentially myelinate electrically active axons via a mechanism dependent on nonsynaptic vesicular release of glutamate.
- Hiroaki Wake
- , Fernando C. Ortiz
- & R. Douglas Fields
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Article
| Open AccessInside-out Ca2+ signalling prompted by STIM1 conformational switch
Depletion of calcium from intracellular stores induces interaction between the endoplasmic reticulum STIM1 protein and the plasma membrane ORAI1 channel that facilitates cellular calcium entry. Here Ma et al. characterize a STIM1 gain-of-function mutant and propose a conformational switch that controls ORAI1 gating.
- Guolin Ma
- , Ming Wei
- & Yubin Zhou
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Opposing calcium-dependent signalling pathways control skeletal muscle differentiation by regulating a chromatin remodelling enzyme
Brg1 is part of the SWI/SNF chromatin remodelling complex that is essential for embryonic development. Here, the authors show that Brg1 is the target of two opposing calcium-regulated molecules involved in myogenesis: calcineurin, which promotes myogenesis, and protein kinase C β (PKCβ), which inhibits it.
- Brian T. Nasipak
- , Teresita Padilla-Benavides
- & Anthony N. Imbalzano
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Article
| Open AccessTonic endocannabinoid-mediated modulation of GABA release is independent of the CB1 content of axon terminals
A simple model for receptor number–function relationships dictates a positive correlation between receptor content and ligand effect. Here, the authors demonstrate that the degree of type-1 cannabinoid receptor (CB1)-modulated GABA release cannot be predicted from CB1content of axon terminals.
- Nora Lenkey
- , Tekla Kirizs
- & Zoltan Nusser
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The mitochondrial uniporter controls fight or flight heart rate increases
Animals react to threats by increasing their heart rate. Wu et al. show that mitochondrial calcium uptake via a highly selective ion channel, the mitochondrial calcium uniporter, stimulates metabolism in cardiac pacemaker cells and is essential for physiological pulse acceleration but not resting heart rate.
- Yuejin Wu
- , Tyler P. Rasmussen
- & Mark E. Anderson
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Mechanism of Ca2+-triggered ESCRT assembly and regulation of cell membrane repair
Mechanical activity predisposes muscle cell membranes to damage, which is repaired by a poorly defined Ca2+-dependent mechanism. Scheffer et al. describe the machinery for Ca2+-induced assembly of ESCRT III membrane remodelling complex at damaged cell membranes, which facilitates repair.
- Luana L. Scheffer
- , Sen Chandra Sreetama
- & Jyoti K. Jaiswal
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Translocation between PI(4,5)P2-poor and PI(4,5)P2-rich microdomains during store depletion determines STIM1 conformation and Orai1 gating
The Orai1 Ca2+ channel is activated by STIM1 in response to Ca2+ release from the ER. Here Maléth et al.show that Orai1 inactivation occurs by translocation to PI(4,5)P2-rich plasma membrane microdomains, which facilitates recruitment of SARAF, a negative regulator of STIM1 function.
- Jozsef Maléth
- , Seok Choi
- & Malini Ahuja
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Structural analyses of Ca2+/CaM interaction with NaV channel C-termini reveal mechanisms of calcium-dependent regulation
Voltage-gated sodium (NaV) channels initiate action potentials in excitable cells and mutations at NaV loci are responsible for several human diseases. Here, Wang et al. provide novel structural insights into the regulation of NaVchannel activity by calcium-bound calmodulin.
- Chaojian Wang
- , Ben C. Chung
- & Geoffrey S. Pitt
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Loss of IP3R-dependent Ca2+ signalling in thymocytes leads to aberrant development and acute lymphoblastic leukemia
Ca2+signalling pathways are known to influence T-cell development and T-cell leukemia progression. Here the authors show that deletion of all three inositol triphosphate receptor homologues in mice severely impairs T-cell development in the thymus and causes spontaneous T-cell acute lymphoblastic leukemia.
- Kunfu Ouyang
- , Rafael Leandro Gomez-Amaro
- & Ju Chen
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| Open AccessMale–female communication triggers calcium signatures during fertilization in Arabidopsis
Fertilization involves species-specific interaction and eventually fusion of two gametic cells, and calcium signalling plays a key role in this process. Here, the authors monitor the changes in intracellular calcium that take place during fertilization of flowering plants and point to specific signatures associated with specific steps of the process.
- Philipp Denninger
- , Andrea Bleckmann
- & Guido Grossmann
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| Open AccessLive imaging of calcium spikes during double fertilization in Arabidopsis
Intracellular calcium waves are key signalling elements during the fertilization process of animals, involved in egg activation. Here the authors image calcium oscillations during the fertilization process in flowering plants, revealing specific signatures involved in the success of this process.
- Yuki Hamamura
- , Moe Nishimaki
- & Tetsuya Higashiyama
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Mid-range Ca2+ signalling mediated by functional coupling between store-operated Ca2+ entry and IP3-dependent Ca2+ release
It remains unclear how localized calcium influx activates distant effectors in the absence of a global Ca2+ rise. Courjaret and Machaca find that mid-range Ca2+ signalling is mediated by coupling between localized store-operated calcium entry and distal IP3-dependent Ca2+ release to activate Cl−channels.
- Raphaël Courjaret
- & Khaled Machaca
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Functional and molecular features of the calmodulin-interacting protein IQCG required for haematopoiesis in zebrafish
NUP98–IQCG is a fusion protein found in acute leukaemia that functions as a regulator of transcriptional expression. Here, Chen et al. investigate IQCG-mediated calcium signalling in haematopoiesis, and propose a model where IQCG can store calmodulin, which once released, activates CaM-dependent kinase IV.
- Li-Ting Chen
- , Wen-Xue Liang
- & Sai-Juan Chen
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Distinct Orai-coupling domains in STIM1 and STIM2 define the Orai-activating site
STIM proteins are key regulators of intracellular Ca2+ signalling. Here, Wang et al. demonstrate that subtle differences between STIM1 and its close homologue STIM2 have profound consequences for their ability to gate Orai1 Ca2+channels, thus revealing the basis for their distinct physiological functions.
- Xizhuo Wang
- , Youjun Wang
- & Donald L Gill
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Article
| Open AccessTriggers of key calcium signals during erythrocyte invasion by Plasmodium falciparum
Plasmodium falciparum reticulocyte-binding protein homologue 1 (PfRH1) and erythrocyte-binding-like protein EBA175 are important for parasite invasion of host cells. Here, Gao et al.show that PfRH1 activates calcium signalling, which induces release of EBA175 and allows junction formation between host cell and parasite.
- Xiaohong Gao
- , Karthigayan Gunalan
- & Peter R. Preiser
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A Ca2+-dependent signalling circuit regulates influenza A virus internalization and infection
Influenza virus can enter host cells through endocytosis, but the molecular pathways involved in this process are not fully understood. Here, the authors dissect these pathways and identify Ca2+as a key regulator of influenza A virus entry via both clathrin-mediated and clathrin-independent endocytosis.
- Yoichiro Fujioka
- , Masumi Tsuda
- & Yusuke Ohba
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Article
| Open AccessMitochondrial calcium uniporter Mcu controls excitotoxicity and is transcriptionally repressed by neuroprotective nuclear calcium signals
Calcium uptake by the mitochondrial calcium uniporter is implicated in excitotoxicity. This study shows that the uniporter gene product mediates mitochondrial calcium uptake and depolarisation in neurons during excitotoxicity, and is transcriptionally repressed by neuroprotective nuclear calcium signals.
- Jing Qiu
- , Yan-Wei Tan
- & Giles E. Hardingham
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| Open AccessCalfacilitin is a calcium channel modulator essential for initiation of neural plate development
Calcium signalling has been implicated in neural induction in the embryo. The authors identify Calfacilitin as a regulator of CaV1.2 calcium channels, which is required for induction of the pre-neural specifiers Geminin and Sox2 in the early chick embryo.
- Costis Papanayotou
- , Irene De Almeida
- & Claudio D. Stern
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Actin-based confinement of calcium responses during Shigella invasion
Shigella triggers an increase in intracellular calcium during invasion of host cells. Here the authors show that increased actin polymerization at the invasion site slows the diffusion of signalling mediators, thus sustaining localized calcium influx at invasion sites.
- Guy Tran Van Nhieu
- , Bing Kai Liu
- & Laurent Combettes
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Activity of the mitochondrial calcium uniporter varies greatly between tissues
The flow of calcium into the mitochondrial matrix is mediated by the mitochondrial calcium uniporter. Fieniet al. apply patch-clamp techniques to mitoplasts isolated from different mouse and Drosophilatissues and find that the mitochondrial calcium uniporter activity varies depending on the tissue studied.
- Francesca Fieni
- , Sung Bae Lee
- & Yuriy Kirichok
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| Open AccessExtracellular Ca2+ is a danger signal activating the NLRP3 inflammasome through G protein-coupled calcium sensing receptors
Levels of extracellular calcium can increase at sites of infection and inflammation; however, the physiological significance of this has been unclear. This work shows that extracellular calcium acts as a danger signal, triggering the NLRP3 inflammasome via two G protein-coupled receptors.
- Manuela Rossol
- , Matthias Pierer
- & Ulf Wagner
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Identification of the functional binding pocket for compounds targeting small-conductance Ca2+-activated potassium channels
Small- and intermediate-conductance K+channels are activated by calcium-bound calmodulin and modulated by small molecules. In this study, a functional binding pocket for the 1-EBIO class of modulators is described and is located at the calmodulin-channel interface.
- Miao Zhang
- , John M. Pascal
- & Ji-Fang Zhang
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| Open AccessRapid calcium-dependent activation of Aurora-A kinase
Aurora-A kinase localizes to centrosomes, is involved in the progression through mitosis and is overexpressed in certain cancers. Here, calcium is shown to induce Aurora-A auto-phosphorylation in a calmodulin-dependent manner, suggesting a novel role for Aurora-A in non-mitotic cells.
- Olga V. Plotnikova
- , Elena N. Pugacheva
- & Erica A. Golemis
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Calmodulin methyltransferase is an evolutionarily conserved enzyme that trimethylates Lys-115 in calmodulin
Calmodulin is a key mediator of calcium-dependent signalling and is subject to post-translational modifications. Here, evolutionarily conserved methyltransferases are identified which trimethylate Lys-115 of calmodulin, implying a broad role in calcium-dependent signalling.
- Roberta Magnani
- , Lynnette M.A. Dirk
- & Robert L. Houtz