Calcium channels articles within Nature Communications

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  • Article
    | Open Access

    TMEM63s are mechanosensitive ion channels activated by hypo-osmolality. Here, the authors determine the cryo-EM structure of mouse TMEM63C confirming its predominant monomeric state and the significance of TM0-TM6 coupling in channel activity.

    • Yuqi Qin
    • , Daqi Yu
    •  & Shangyu Dang

  • Article
    | Open Access

    The intermembrane complexes mediating calcium signals are crucial but poorly understood. Here the authors identify a Phe-His pair in the calcium-sensing STIM1 protein that controls both activation and pairing of STIM1 with Orai channels to generate calcium signals

    • Yandong Zhou
    • , Michelle R. Jennette
    •  & Donald L. Gill

  • Article
    | Open Access

    Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular Ca2+ channels that produce Ca2+ oscillations in response to GPCR and RTK activation. Here, Paknejad et al. resolve the conformational landscape of IP3Rs that gives rise to the biphasic dependence on Ca2+ for channel activity.

    • Navid Paknejad
    • , Vinay Sapuru
    •  & Richard K. Hite

  • Comment
    | Open Access

    In this work, Morgenstern and colleagues describe an approach involving functionalized nanobodies which decrease the activity of voltage-gated Ca2+ channels associated with β1 subunits and promote their removal from the surface membrane of neurons and muscle.

    • Declan Manning
    •  & L. Fernando Santana

  • Article
    | Open Access

    Auxiliary subunit molecular diversity is an unexploited target for developing ion channel inhibitors. Here, the authors develop a general approach to inhibit ion channels based on the resident auxiliary subunit isoform to elucidate unique functions of distinct ion channel macromolecular complexes.

    • Travis J. Morgenstern
    • , Neha Nirwan
    •  & Henry M. Colecraft

  • Article
    | Open Access

    This study demonstrates that the curvature of the cell membrane directly regulates the spatial distribution of Piezo1, a widely expressed mechanosensitive ion channel. Piezo1 may flatten upon activation and can mechanically inhibit membrane dynamics

    • Shilong Yang
    • , Xinwen Miao
    •  & Zheng Shi

  • Article
    | Open Access

    Sperm motility and male fertility requires function of the CatSper calcium channels. Here, using cryo-electron tomography, authors visualize the native in-cell 3D structure and higher-order organization of the CatSper as long zigzag rows along the sperm tail.

    • Yanhe Zhao
    • , Huafeng Wang
    •  & Jean-Ju Chung

  • Article
    | Open Access

    T-type calcium channels are implicated in many diseases. Here, multiple structures of CaV3.3 channel elucidate molecular mechanisms of T-type CaV channels activation at low voltage and interaction with different clinically used channel blockers.

    • Lingli He
    • , Zhuoya Yu
    •  & Yan Zhao

  • Article
    | Open Access

    IP3 receptors are intracellular calcium channels involved in numerous signaling pathways. Here, the authors present the cryo-EM structures of type-3 IP3 receptors in multiple gating conformations, including the active state revealing the molecular mechanism of the receptor activation.

    • Emily A. Schmitz
    • , Hirohide Takahashi
    •  & Erkan Karakas

  • Article
    | Open Access

    Nicotinic acid adenine dinucleotide phosphate (NAADP) potent Ca2+ mobilizing second messenger which uniquely triggers Ca2+ release from acidic endolysosomal organelles. Here the authors identify Lsm12 as an NAADP receptor essential for NAADP-evoked Ca2+ release from lysosomes via NAADP binding on its Lsm domain.

    • Jiyuan Zhang
    • , Xin Guan
    •  & Jiusheng Yan

  • Article
    | Open Access

    ORAI3 is part of pore forming calcium channels involved in T cell activation. Here the authors show that there is increased expression of ORAI3 in T cells from patients with rheumatoid arthritis and that the transcription factor IKAROS negatively regulates the ORAI3 promoter, indicating a regulatory loop that can control auto-reactivity of T cells in these patients.

    • Zhongde Ye
    • , Yi Shen
    •  & Jörg J. Goronzy

  • Article
    | Open Access

    Ryanodine Receptors (RyRs) release Ca2+ from the endoplasmic and sarcoplasmic reticulum. Mutations in RyR are linked to malignant hyperthermia (MH), myopathies, and arrhythmias. Here, a collection of cryoEM structures provides insights into the molecular consequences of MHrelated RyR mutation R615C, and how apoCaM opens RyR1.

    • Kellie A. Woll
    • , Omid Haji-Ghassemi
    •  & Filip Van Petegem

  • Article
    | Open Access

    Combining cryo-electron tomography with subtomogram averaging (StA) allows the in situ structure determination of proteins and protein complexes. Here, the authors present the hybrid StA (hStA) workflow that combines the advantages of single particle cryo-EM and StA and consists of a tomographic data collection scheme and a data processing workflow and they demonstrate how hStA can improve the resolution using two examples: the ion channel RyR1 and tobacco mosaic virus.

    • Ricardo M. Sanchez
    • , Yingyi Zhang
    •  & Mikhail Kudryashev

  • 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

    CASTOR is a Lotus japonicus ion channel required for nuclear Ca2+ spiking and establishing rhizobial and mycorrhizal symbioses. Here, via structural and functional analysis, Kim et al. show that CASTOR is a Ca2+-selective channel activated via Ca2+ binding to a soluble gating ring consisting of tandem RCK domains.

    • Sunghoon Kim
    • , Weizhong Zeng
    •  & Youxing Jiang

  • Article
    | Open Access

    Endoplasmic reticulum Ca2+ sensing STIM proteins and plasma membrane Orai1 channels together regulate Ca2+ influx in eukaryotic cells. Here authors show that two Ca2+-dependent transcription factors, NFAT1 and c-fos, have different requirements for the number of STIM1-Orai1 clusters and on the Ca2+ flux through the clusters.

    • Yu-Ping Lin
    • , Daniel Bakowski
    •  & Anant B. Parekh

  • Article
    | Open Access

    Piezo channels are mechanosensitive and rely on membrane composition to transduce physical stimuli into electrical signals. Here authors analyse the membrane components that modulate Piezo1 function using lipid profiling which shows that fatty acid metabolism can modulate ion channel activity.

    • Luis O. Romero
    • , Andrew E. Massey
    •  & Valeria Vásquez

  • Article
    | Open Access

    Two-photon absorption capacity of azobenzene photoswitches usually comes with a reduction in thermal stability. Here, the authors developed photoswitches with high two-photon sensitivity and enhanced cis isomer thermal lifetime for the control of glutamate receptors.

    • Gisela Cabré
    • , Aida Garrido-Charles
    •  & Ramon Alibés

  • Article
    | Open Access

    In plants, hyperosmolality stimuli triggers opening of the osmosensitive channels, leading to a rapid downstream signaling cascade. Here, the authors solve the cryo-EM structure of an osmosensitive channel from Arabidopsis OSCA1.2 in its inactivated state.

    • Xin Liu
    • , Jiawei Wang
    •  & Linfeng Sun

  • Article
    | Open Access

    Giant cell lesions of the jaw (GCLJ) are debilitating benign tumors of unclear origin. The authors identify driver recurrent somatic mutations in TRPV4, KRAS and FGFR1 and show they converge on aberrant activation of the MAPK pathway. Their findings extend the spectrum of TRPV4 channelopathies and provide rationale for targeted therapies at the bedside in GCLJ.

    • Carolina Cavalieri Gomes
    • , Tenzin Gayden
    •  & Nada Jabado

  • Article
    | Open Access

    Manipulation of the pancreas during surgery can induce acute pancreatitis due to zymogen activation. Here the authors show that the mechanoreceptor Piezo1 is activated by pressure and its activation leads to calcium dependent pancreatic injury whereas its inhibition is protective against pancreatitis.

    • Joelle M.-J. Romac
    • , Rafiq A. Shahid
    •  & Rodger A. Liddle

  • Article
    | Open Access

    Polycystic kidney disease 2-like 1 protein (PKD2L1) is a voltage-dependent calcium-dependent nonselective ion channel involved in sour taste perception and regulation of pH-dependent action potential of spinal cord neurons. Here the authors present the 3.4 Å cryo-EM structure of PKD2L1 in the open state and propose a model for the gating mechanism.

    • Qiang Su
    • , Feizhuo Hu
    •  & Tingliang Wang

  • 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

    Mutations in the RyR1 channel cause core myopathies. Here the authors show that ER stress and the unfolded protein response underlie the pathology caused by a common RyR1 channel mutation, and show that treatment with a chemical chaperone restores muscle function in mice.

    • Chang Seok Lee
    • , Amy D. Hanna
    •  & Susan L. Hamilton

  • Article
    | Open Access

    Store-operated Ca2+channels (CRAC) are involved in several cellular functions. Here the authors identify a hydrophobic gate in the CRAC pore and show that CRAC activation by STIM1 involves rotation of the pore helix that hydrates this region to allow ion passage through the pore.

    • Megumi Yamashita
    • , Priscilla S.-W. Yeung
    •  & Murali Prakriya

  • 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

    Measuring thein vivo stoichiometry of protein-protein interactions is challenging. Here the authors take a FRET-based approach, quantifying stoichiometry based on ratiometric comparison of donor and acceptor fluorescence, and apply their method to report on a Ca2+-induced switch in calmodulin binding to Ca2+ion channels.

    • Manu Ben-Johny
    • , Daniel N. Yue
    •  & David T. Yue

  • Article
    | Open Access

    Phosphorylation of L-type calcium CaV channels by protein kinase A is essential for several physiological events. Here, the authors show how this kinase regulates CaV1.4 activity, suggesting a general regulatory mechanism for all L-type calcium channels.

    • Lingjie Sang
    • , Ivy E. Dick
    •  & David T. Yue

  • Article
    | Open Access

    The identity of mechanosensors within aortic baroreceptors that sense fluctuations in blood pressure is unclear. Here, Lau et al.show that a cation channel TRPC5 acts as a transducer of mechanical stimuli in aortic baroreceptor neurons in rodents.

    • On-Chai Lau
    • , Bing Shen
    •  & Xiaoqiang Yao

  • 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

  • Article
    | Open Access

    Microvilli on epithelial cells can sense the surrounding fluid environment, but the regulatory mechanism behind their formation is mostly unknown. Here Miura et al.show that fluid shear stress serves as a trigger for microvilli formation via activation of the calcium ion channel TRPV6.

    • Shigenori Miura
    • , Koji Sato
    •  & Shoji Takeuchi

  • Article
    | Open Access

    STIM1, the endoplasmic reticulum calcium sensor, is activated in response to calcium store depletion and translocates to the ER–plasma membrane junctions to activate Orai1 channels. Here the authors present a new model of unimolecular coupling between STIM1 and Orai1 whereby STIM1 dimers may be involved in crosslinking Orai1 channels.

    • Yandong Zhou
    • , Xizhuo Wang
    •  & Donald L. Gill

  • Article |

    The plasma membrane Ca2+ channel ORAI1 is gated directly by the ER-resident protein STIM1. Here Gudlur et al. show that STIM1 elicits conformational changes near the extracellular opening of the channel, involving the Ca2+-binding residue E106 and the pore-lining residue V102, which forms a barrier to ion conduction in the closed state.

    • Aparna Gudlur
    • , Ariel Quintana
    •  & Patrick G. Hogan

  • Article
    | Open Access

    Single molecule fluorescence microscopy is a powerful technique to study protein dynamics in cells, but it has not been applied to adult animals. The authors use complementation-activated light microscopy in C. elegansto discover that dystrophin regulates the diffusion properties of voltage-dependent calcium ion channels at the surface of body-wall muscle cells.

    • Hong Zhan
    • , Ramunas Stanciauskas
    •  & Fabien Pinaud

  • Article
    | Open Access

    Compound 8-1-(3-chlorophenethyl)-3-cyclopentylpyrimidine-2,4,6(1H,3H,5H)-trione was previously reported to be a selective inhibitor of the CaV1.3 calcium channel. Now, Huang et al. demonstrate that selectivity towards CaV1.3 relative to CaV1.2 is dependent on the type of β-subunit and CaV1.3 splice variant assayed.

    • Hua Huang
    • , Cheng Yang Ng
    •  & Tuck Wah Soong

  • Article
    | Open Access

    Mutations in the fragile X mental retardation protein are implicated in synaptic dysfunction in fragile X syndrome. Here, Ferron et al. show that fragile X mental retardation protein maintains proper neurotransmission by regulating the density of N-type calcium channels in the presynaptic terminal.

    • Laurent Ferron
    • , Manuela Nieto-Rostro
    •  & Annette C. Dolphin

  • Article
    | Open Access

    When endoplasmic reticulum calcium levels are low, STIM1 binds to and opens Orai1 channels in the plasma membrane to replenish calcium stores. Stathopulos et al.present solution structures of the STIM1 coiled-coil domain in the presence and absence of Orai1, revealing the structural basis for this interaction.

    • Peter B. Stathopulos
    • , Rainer Schindl
    •  & Mitsuhiko Ikura

  • Article |

    Calcium channel blockers are used as treatments for hypertension, angina and pain. Yang et al.show that diverse cytosolic calcium channel-binding proteins act as blockers when targeted to the plasma membrane, and suggest how this property might be used to screen for small-molecule inhibitors.

    • Tingting Yang
    • , Lin-Ling He
    •  & Henry M. Colecraft

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