Article
|
Open Access
Featured
-
-
Article
| Open AccessElucidation of the structural basis for ligand binding and translocation in conserved insect odorant receptor co-receptors
Insects rely on olfaction for behavior control. Recent structural studies of receptors provide insight into ligand binding. Here, the authors identify dynamic binding mechanism to Orco, explaining its high selectivity with insights in compound screening.
- Jody Pacalon
- , Guillaume Audic
- & Jérémie Topin
-
Article
| Open AccessSegregated cation flux by TPC2 biases Ca2+ signaling through lysosomes
TPC2 is a lysosomal ion channel permeable to both calcium and sodium ions. Here, the authors show that TPC2 can selectively increase its calcium permeability when simultaneously challenged by both its natural activators- NAADP and PI(3,5)P2.
- Yu Yuan
- , Dawid Jaślan
- & Sandip Patel
-
Article
| Open AccessInhibition mechanism of the chloride channel TMEM16A by the pore blocker 1PBC
TMEM16A, a calcium-activated chloride channel involved in multiple cellular processes, is implicated in various diseases, but its pharmacology remains poorly understood. Here, the authors combine cryo-EM and electrophysiology to elucidate the mechanism of TMEM16A inhibition by the pore blocker 1PBC.
- Andy K. M. Lam
- , Sonja Rutz
- & Raimund Dutzler
-
Article
| Open AccessIntrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2
A key question in mechanobiology is how mechanical forces are transmitted to PIEZO ion channels. Here, Verkest et al. identify an intracellular channel domain that is required for the activation of PIEZO2 by cytoskeleton-transmitted forces.
- Clement Verkest
- , Irina Schaefer
- & Stefan G. Lechner
-
Article
| Open AccessIn vivo spatiotemporal control of voltage-gated ion channels by using photoactivatable peptidic toxins
Photoactivable toxins targeting ion channels have great potential to control cell activity. Here the authors report HwTxIV-Nvoc, a UV light-cleavable and photoactivatable peptide that targets voltage-gated sodium channels; they validate this in cells, brain slices and in vivo on mice neuromuscular junctions.
- Jérôme Montnach
- , Laila Ananda Blömer
- & Michel De Waard
-
Article
| Open AccessStructural determinants and regulation of spontaneous activity in GABAA receptors
GABAA receptors (GABAARs) cause inhibition in the brain by functioning as heteropentamers formed from multiple subunit types. Here, the authors demonstrate that receptors incorporating β3 subunits can spontaneously gate, which is modulated by protein kinases and neurosteroids to affect tonic inhibition.
- Craig A. Sexton
- , Reka Penzinger
- & Trevor G. Smart
-
Article
| Open AccessAutomatic deep learning-driven label-free image-guided patch clamp system
Patch clamp recording of neurons is slow and labor-intensive. Here the authors present a method for automated deep learning driven label-free image guided patch clamp physiology to perform measurements on hundreds of human and rodent neurons.
- Krisztian Koos
- , Gáspár Oláh
- & Peter Horvath
-
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
-
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
-
Article
| 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
-
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
-
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
-
Article
| Open AccessElectrical behaviour of dendritic spines as revealed by voltage imaging
Dendritic spines located on individual neurons process information, but our understanding of the electrical behaviour of spines is still limited. Here, the authors use voltage-sensitive dye imaging techniques to monitor electrical signals from thin basal spines and show that synapses are not electrically isolated by the spine neck.
- Marko A. Popovic
- , Nicholas Carnevale
- & Dejan Zecevic
-
Article
| Open AccessErrors in the measurement of voltage-activated ion channels in cell-attached patch-clamp recordings
Voltage-activated ion channels can be measured in neurons using the cell-attached patch-clamp technique. Williams and Wozny show that this technique is prone to errors that are caused by the flow of current through the ion channels; a method to correct for these discrepancies is described.
- Stephen R. Williams
- & Christian Wozny