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| Open AccessPathological conformations of disease mutant Ryanodine Receptors revealed by cryo-EM
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
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Article
| Open Access3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics
Currently technologies for monitoring and controlling neural activities in 3D models are lacking. Here the authors report a 3D high-density multielectrode array, with optical stimulation and drug delivery, to investigate neural circuit dynamics in engineered 3D neural tissues.
- Hyogeun Shin
- , Sohyeon Jeong
- & Il-Joo Cho
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Article
| Open AccessPKA drives an increase in AMPA receptor unitary conductance during LTP in the hippocampus
Long-term potentiation at hippocampal CA1 synapses can be due to increasing the number and/or single-channel conductance of AMPA receptors. The authors show that PKA and CaMKII are necessary and together sufficient to increase single channel conductance, via insertion of calcium-permeable AMPA receptors.
- Pojeong Park
- , John Georgiou
- & Graham L. Collingridge
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Article
| Open AccessStructure and dynamics of the drug-bound bacterial transporter EmrE in lipid bilayers
The small proton-coupled transporter EmrE confers multidrug resistance in bacteria. The structure of drug-bound EmrE in phospholipid bilayers is now determined using solid-state NMR. The structure provides detailed insights into the molecular mechanism of substrate recognition by this transporter.
- Alexander A. Shcherbakov
- , Grant Hisao
- & Mei Hong
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Article
| Open AccessThe structural basis of promiscuity in small multidrug resistance transporters
Gdx-Clo is a bacterial transporter from the small multidrug resistance (SMR) family. Here, the authors use solid supported membrane electrophysiology to characterize Gdx-Clo functionally and report crystal structures of Gdx-Clo which confirm the dual topology architecture and offer insight into substrate binding and transport mechanism.
- Ali A. Kermani
- , Christian B. Macdonald
- & Randy B. Stockbridge
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Article
| Open AccessBrainPhys neuronal medium optimized for imaging and optogenetics in vitro
Current media for neuronal cell and organoid cultures are suboptimal for functional imaging and optogenetics experiments, owing to phototoxicity and unphysiological performance. Here the authors formulate an optimised neuronal medium to support live cell imaging and electrophysiological activity.
- Michael Zabolocki
- , Kasandra McCormack
- & Cedric Bardy
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Article
| Open AccessVersatile live-cell activity analysis platform for characterization of neuronal dynamics at single-cell and network level
Current methods of neuronal network imaging cannot be used for continuous, long-term functional recordings. Here, the authors present a dual-mode high-density microelectrode array, which can simultaneously record in full-frame and high-signal-to-noise modes for label-free electrophysiological measurements.
- Xinyue Yuan
- , Manuel Schröter
- & Urs Frey
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Article
| Open AccessFully organic compliant dry electrodes self-adhesive to skin for long-term motion-robust epidermal biopotential monitoring
Reported wearable dry electrodes have limited long-term use due to their imperfect skin compliance and high motion artifacts. Here, the authors report an intrinsically conductive, stretchable polymer dry electrode with excellent self-adhesiveness for long-term high-quality biopotential detection.
- Lei Zhang
- , Kirthika Senthil Kumar
- & Jianyong Ouyang
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Article
| Open AccessPrintable microscale interfaces for long-term peripheral nerve mapping and precision control
Modulation of peripheral nervous system signalling has many applications in medicine, neurobiology and machine-man interfaces. Here the authors develop a microscale implantable device for chronic interfacing with a small diameter nerve, and show multi-week in vivo recording and control of activity.
- Timothy M. Otchy
- , Christos Michas
- & Timothy J. Gardner
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Article
| Open AccessEEG microstates are a candidate endophenotype for schizophrenia
EEG microstate abnormalities have been reported in patients with schizophrenia. Here the authors demonstrate that patients and their siblings show similar microstate abnormalities compared to healthy controls.
- Janir Ramos da Cruz
- , Ophélie Favrod
- & Michael H. Herzog
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Article
| Open AccessChemical modification of proteins by insertion of synthetic peptides using tandem protein trans-splicing
Chemical modification of proteins can be used to decipher function or use that function for therapeutic purposes. Here, the authors insert synthetic peptides via tandem protein trans-splicing to add post-translational modifications or non-canonical amino acids.
- K. K. Khoo
- , I. Galleano
- & S. A. Pless
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Article
| Open AccessIntegrating electric field modeling and neuroimaging to explain inter-individual variability of tACS effects
Electrical stimulation of the brain can have variable effects, perhaps because of individual differences in brain structure which produce differences in the electric fields. Here, the authors show that using functional and structural brain imaging along with electric field modeling can predict the effectiveness of stimulation.
- Florian H. Kasten
- , Katharina Duecker
- & Christoph S. Herrmann
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Article
| Open AccessSingle-molecule sensing of peptides and nucleic acids by engineered aerolysin nanopores
Aerolysin pores have potential to improve the accuracy of DNA sequencing and single-molecule proteomics. Here, the authors rationally design a set of mutated pores to achieve a more accurate detection of peptides and nucleic acids.
- Chan Cao
- , Nuria Cirauqui
- & Matteo Dal Peraro
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Article
| Open AccessAugmentation of myocardial If dysregulates calcium homeostasis and causes adverse cardiac remodeling
The depolarizing funny current contributing to cardiac pacemaking is upregulated in the myocardium of failing and infarcted hearts, but whether the current is implied in disease mechanisms is unclear. Here the authors generate HCN4 transgenic mice and show that upregulation of funny current to the levels observed in human heart failure alters calcium homeostasis leading to cardiac remodelling and arrhythmia.
- Pessah Yampolsky
- , Michael Koenen
- & Patrick A. Schweizer
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| Open AccessActivating an anterior nucleus gigantocellularis subpopulation triggers emergence from pharmacologically-induced coma in rodents
The reticular activating system (RAS) of the brainstem regulates wakefulness, and stimulation of RAS areas can reverse effects of anaesthesia. Here, the authors show that stimulation of a particular RAS area, the anterior portion of nucleus gigantocellularis, can produce arousal from deep coma.
- S. Gao
- , A. Proekt
- & D. W. Pfaff
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Article
| Open AccessNeural effects of transcranial magnetic stimulation at the single-cell level
Transcranial Magnetic Stimulation (TMS) can modulate human brain activity, but the extent of the cortical area activated by TMS is unclear. Here, the authors show that TMS affects monkey single neuron activity in an area less than 2 mm diameter, while TMS-induced activity and task-related activity do not summate.
- Maria C. Romero
- , Marco Davare
- & Peter Janssen
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Article
| Open AccessElectric field dynamics in the brain during multi-electrode transcranial electric stimulation
Transcranial alternating current stimulation (TACS) of the brain is widely used in neuroscience, but the electric fields produced when multiple stimulation electrodes are used are not well understood. Here, the authors directly record electric fields in primate brains during multi-electrode TACS.
- Ivan Alekseichuk
- , Arnaud Y. Falchier
- & Alexander Opitz
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Article
| Open AccessRecollection in the human hippocampal-entorhinal cell circuitry
The hippocampus is involved both in episodic memory recall and scene processing. Here, the authors show that hippocampal neurons first process scene cues before coordinating memory-guided pattern completion in adjacent entorhinal cortex.
- Bernhard P. Staresina
- , Thomas P. Reber
- & Florian Mormann
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| Open AccessCa2+-dependent regulation of sodium channels NaV1.4 and NaV1.5 is controlled by the post-IQ motif
Skeletal muscle voltage-gated Na+ channel (NaV1.4) activity is subject to calmodulin (CaM) mediated Ca2 +-dependent inactivation while cardiac NaV1.5 is not. Here authors use structural biology, binding and electrophysiology to parse the Ca2 +-dependent changes of CaM when bound to the NaV1.4.
- Jesse B. Yoder
- , Manu Ben-Johny
- & L. Mario Amzel
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Article
| Open AccessIntrinsic functional architecture of the non-human primate spinal cord derived from fMRI and electrophysiology
Resting-state fMRI shows networks of correlated activity in the spinal cord, similar to those in the brain, but whether fMRI is a valid measure of functional connectivity in spinal cord is unclear. Here, the authors show that fMRI corresponds well to electrophysiological measures of spinal cord activity.
- Tung-Lin Wu
- , Pai-Feng Yang
- & John C. Gore
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Article
| Open AccessDiscovery of key whole-brain transitions and dynamics during human wakefulness and non-REM sleep
Sleep is composed of a number of different stages, each associated with a different pattern of brain activity. Here, using a data-driven Hidden Markov Model (HMM) of fMRI data, the authors discover a more complex set of neural activity states underlying the conventional stages of non-REM sleep.
- A. B. A. Stevner
- , D. Vidaurre
- & M. L. Kringelbach
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Article
| Open AccessDeep brain activities can be detected with magnetoencephalography
Magnetoencephalography (MEG) is a non-invasive method of measuring neural activity but the hippocampus and amygdala are difficult to measure with MEG because of their deep localization. Here, the authors show with simultaneous MEG and invasive recordings that hippocampus and amygdala activity can be retrieved from the surface.
- Francesca Pizzo
- , N. Roehri
- & C. G. Bénar
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Article
| Open AccessHigh-speed mechano-active multielectrode array for investigating rapid stretch effects on cardiac tissue
While strain is known to affect cardiac electrophysiology, experimental systems to interrogate the effect of rapid strain cycles on cardiac tissue are lacking. Here the authors introduce a multielectrode array that can induce rapid dynamic strain cycles on cardiomyocyte strands and see effects of strain amplitude but not strain rate on impulse conduction.
- Matthias Imboden
- , Etienne de Coulon
- & Stephan Rohr
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| Open AccessMutation of a single residue promotes gating of vertebrate and invertebrate two-pore domain potassium channels
Mutations that modulate the activity of ion channels are essential tools to understand the biophysical determinants that control their gating. Here authors reveal the role played by a single residue in the second transmembrane domain of vertebrate and invertebrate two-pore domain potassium channels.
- Ismail Ben Soussia
- , Sonia El Mouridi
- & Thomas Boulin
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Article
| Open AccessSubcortical electrophysiological activity is detectable with high-density EEG source imaging
Electroencephalography (EEG) allows the measurement of electrical signals associated with brain activity, but it is unclear if EEG can accurately measure subcortical activity. Here, the authors show that source dynamics, reconstructed from scalp EEG, correlate with activity recorded from human thalamus and nucleus accumbens.
- Martin Seeber
- , Lucia-Manuela Cantonas
- & Christoph M. Michel
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Article
| Open AccessDifferential influences of environment and self-motion on place and grid cell firing
Place cells and grid cells are known to encode spatial information about an animal’s location relative to the surrounding environment. Here, the authors show that place cells predominantly encode environmental sensory inputs, while grid cell activity reflects a greater influence of physical motion.
- Guifen Chen
- , Yi Lu
- & Neil Burgess
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Article
| Open AccesstACS motor system effects can be caused by transcutaneous stimulation of peripheral nerves
Transcranial alternating current stimulation (tACS) uses weak electrical currents, applied to the head, to modulate brain activity. Here, the authors show that contrary to previous assumptions, the effects of tACS on the brain may be mediated by its effect on peripheral nerves in the skin, not direct.
- Boateng Asamoah
- , Ahmad Khatoun
- & Myles Mc Laughlin
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Article
| Open AccessThe mediodorsal pulvinar coordinates the macaque fronto-parietal network during rhythmic spatial attention
Recent evidence shows that spatial attention is discontinuous over time, sampling locations in rhythmic cycles (3–6 Hz). Here, the authors show that the pulvinar has a role in coordinating this rhythmic sampling, with neural activity propagating from pulvinar to cortex during periods of engagement.
- Ian C. Fiebelkorn
- , Mark A. Pinsk
- & Sabine Kastner
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Article
| Open AccessChanging temporal context in human temporal lobe promotes memory of distinct episodes
Memories formed around the same time are linked together by a shared temporal context. Here, the authors show that the ability to selectively retrieve distinct episodic memories formed close together in time is related to how quickly neural representations of temporal context change over time during encoding.
- Mostafa M. El-Kalliny
- , John H. Wittig Jr
- & Kareem A. Zaghloul
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Article
| Open AccessMedial temporal lobe functional connectivity predicts stimulation-induced theta power
Direct electrical brain stimulation can induce widespread changes in neural activity, offering a means to modulate network-wide activity and treat disease. Here, the authors show that the low-frequency functional connectivity profile of a stimulation target predicts where induced theta activity occurs.
- E. A. Solomon
- , J. E. Kragel
- & M. J. Kahana
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Article
| Open AccessA microfabricated nerve-on-a-chip platform for rapid assessment of neural conduction in explanted peripheral nerve fibers
Peripheral nerves have a complex physiology and it is therefore difficult to measure axonal activity in vitro. Here the authors make a nerve-on-a-chip platform to align peripheral nerves and permit measurement of conduction amplitude and velocity along several axons in a single experiment.
- Sandra Gribi
- , Sophie du Bois de Dunilac
- & Stéphanie P. Lacour
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Article
| Open AccessModular engineering to increase intracellular NAD(H/+) promotes rate of extracellular electron transfer of Shewanella oneidensis
A bottleneck for the application of bioelectrochemical systems is the slow rate of extracellular electron transfer. Here the authors use a synthetic biology approach to redirect metabolic flux to NAD+ biosynthesis, which enhances the intracellular electron flux and the extracellular electron transfer rate.
- Feng Li
- , Yuan-Xiu Li
- & Hao Song
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Article
| Open AccessATP activates bestrophin ion channels through direct interaction
Human Bestrophin1 (hBest1), a calcium-activated chloride channel in retinal pigment epithelium (RPE), is essential for retina physiology. Using electrophysiological and structural approaches, the authors uncover an ATP-dependent activation mechanism of hBest1, and identify an ATP-binding motif.
- Yu Zhang
- , Alec Kittredge
- & Tingting Yang
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Article
| Open AccessSoft transparent graphene contact lens electrodes for conformal full-cornea recording of electroretinogram
The electrical response of the eye to optical stimulus is important in disease diagnosis but current electrodes used have limitations. Here, the authors report on the development of soft transparent graphene-based contact lens electrodes for electroretinogram recording and test the device in vivo.
- Rongkang Yin
- , Zheng Xu
- & Xiaojie Duan
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| Open AccessProbing the gating mechanism of the mechanosensitive channel Piezo1 with the small molecule Yoda1
Piezo ion channels transduce mechanical stimuli into biological signals but the underlying mechanism has remained elusive. Here, the authors use the selective agonist Yoda1 to identify molecular determinants of Piezo activation, providing mechanistic insights into Piezo-mediated mechanotransduction.
- Jerome J. Lacroix
- , Wesley M. Botello-Smith
- & Yun Luo
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Article
| Open AccessThalamocortical dysrhythmia detected by machine learning
Thalamocortical dysrhythmia has been proposed to occur in a number of neurological and psychiatric disorders. Here, the authors use a data-driven approach to demonstrate thalamocortical dysrhythmia occurs in individuals with Parkinson’s disease, neuropathic pain, tinnitus, and depression.
- Sven Vanneste
- , Jae-Jin Song
- & Dirk De Ridder
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Article
| Open AccessMulti-day rhythms modulate seizure risk in epilepsy
The ability to identify periods of heightened seizure risk could enable new treatments for patients with epilepsy. Here, the authors describe long term EEG recordings from 37 patients which allow them to identify multi-day fluctuations in interictal activity.
- Maxime O. Baud
- , Jonathan K. Kleen
- & Vikram R. Rao
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Article
| Open AccessBri2 BRICHOS client specificity and chaperone activity are governed by assembly state
The BRICHOS domain is a chaperone that can act against amyloid-β peptide fibril formation and non-fibrillar protein aggregation. Here the authors use a multidisciplinary approach and show that the Bri2 BRICHOS domain has qualitatively different chaperone activities depending on its quaternary structure.
- Gefei Chen
- , Axel Abelein
- & Jan Johansson
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Article
| Open AccessRhythmic potassium transport regulates the circadian clock in human red blood cells
Circadian rhythms usually rely on cyclic variations in gene expression. Red blood cells, however, display circadian rhythms while being devoid of nuclear DNA. Here, Henslee and colleagues show that circadian rhythms in isolated human red blood cells are dependent on rhythmic transport of K+ ions.
- Erin A. Henslee
- , Priya Crosby
- & Fatima H. Labeed
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Article
| Open AccessOscillatory brain activity in spontaneous and induced sleep stages in flies
Sleep in mammals comprises physiologically and functionally distinct stages. Here, the authors report a transitional sleep stage in Drosophila associated with 7–10 Hz oscillatory activity that can be obtained through activation of the sleep-promoting neurons of the dorsal fan-shaped body.
- Melvyn H. W. Yap
- , Martyna J. Grabowska
- & Bruno van Swinderen
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Article
| Open AccessA very large-scale microelectrode array for cellular-resolution electrophysiology
Large electronics limit low-noise, non-invasive electrophysiological measurements to a thousand simultaneously recording channels. Here the authors build an array of 65k simultaneously recording and stimulating electrodes and use it to sort and classify single neurons across the entire mouse retina.
- David Tsai
- , Daniel Sawyer
- & Kenneth L. Shepard
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Article
| Open AccessNanopore electric snapshots of an RNA tertiary folding pathway
While RNA folding is critical for its function, study of this process is challenging. Here, the authors combine nanopore single-molecule manipulation with theoretical analysis to follow the folding of an RNA pseudoknot, monitoring the intermediate states and the kinetics of their interconversion.
- Xinyue Zhang
- , Dong Zhang
- & Li-Qun Gu
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Article
| Open AccessLow frequency transcranial electrical stimulation does not entrain sleep rhythms measured by human intracranial recordings
Transcranial alternating current stimulation (tACS) has been proposed to enhance neural rhythms supporting memory. Here, the authors leverage human intracranial recordings to show that low-frequency tACS does not entrain key rhythms in non-REM sleep or resting wakefulness.
- Belen Lafon
- , Simon Henin
- & Anli A. Liu
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Article
| Open AccessInverted battery design as ion generator for interfacing with biosystems
At the molecular level, biological activities involve the transport of ions in a system. Here the authors demonstrate an ‘electron battery’ by inverting the configuration of a traditional Li-ion battery to generate an ionic current to interact with a biosystem for potential biomedical applications.
- Chengwei Wang
- , Kun (Kelvin) Fu
- & Liangbing Hu
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Article
| Open AccessA connexin30 mutation rescues hearing and reveals roles for gap junctions in cochlear amplification and micromechanics
A point mutation in the gap-junction protein connexin 30 stops early onset age-related hearing loss. Here, the authors show that gap junctions contribute to cochlear micromechanics and that cochlear amplification is likely controlled by extracellular potentials in vicinity of the cochlear sensory cells.
- Victoria A. Lukashkina
- , Snezana Levic
- & Ian J. Russell
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Article
| Open AccessA quantized mechanism for activation of pannexin channels
Pannexins are oligomeric plasma membrane channels that allow permeation of ions and large molecules. Here the authors show that human Pannexin 1 activation is a multistep event, where modification of each monomer opens the channel to a unique conductance state and fine tunes its activity.
- Yu-Hsin Chiu
- , Xueyao Jin
- & Douglas A. Bayliss
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Article
| Open AccessKCNE1 induces fenestration in the Kv7.1/KCNE1 channel complex that allows for highly specific pharmacological targeting
Specificity of inhibitors of voltage-gated ion channels is crucial for their use as therapeutics. Here, the authors show that adamantane derivatives interact with a specific binding site on fenestrations that only become available when accessory subunits are bound to the channel.
- Eva Wrobel
- , Ina Rothenberg
- & Guiscard Seebohm
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Article
| Open AccessNicotinamide is an endogenous agonist for a C. elegans TRPV OSM-9 and OCR-4 channel
TRPV are cation channels activated by physical and chemical stimuli. Here the authors show that nicotinamide is a soluble, endogenous agonist for orthologous TRPV channels fromC. elegans and Drosophila, unveiling a metabolic-based regulation for TRPV channel activity.
- Awani Upadhyay
- , Aditya Pisupati
- & Wendy Hanna-Rose
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Article
| Open AccessStructural and functional characterization of a calcium-activated cation channel from Tsukamurella paurometabola
Tetrameric cationic channels specificity is determined by the sequence and structural conformation of their selectivity filter. Here, the authors show that a cationic channel from Tsukamurella paurometabola is non-selective due to a Ca2+-binding motif within its unusual proline-rich filter.
- Balasundaresan Dhakshnamoorthy
- , Ahmed Rohaim
- & Benoît Roux