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Article
Meyer B. Jackson, Chung-Wei Chiang, Jinbo Cheng
The impact of fusion pores on synaptic release is difficult to discern. Through analysis of miniature excitatory synaptic currents, Jackson et al. revealed a correlation between amplitude and rise-time. Modeling indicated this correlation results from the interplay between vesicle size and fusion pore flux.
Article
Mie Gangi, Takuma Maruyama, Toshiyuki Ishii, Makoto Kaneda
ON and OFF signals in the retina are processed via parallel pathways. Gangi et al. reveal that regulation of starburst amacrine cells, which are crucial for motion detection, is different between the ON and OFF pathways, despite their morphological mirror symmetry.
Article
Olle Rönnelid, Fredrik Elinder
In a screen of 10,000 compounds, Ronnelid and Elinder found that carboxyl-group–containing compounds are potent activators of voltage-gated potassium channels. They suggest that lipophilic and charged compounds electrostatically activate the channel by binding close to the channel’s voltage sensor.
Article
Pengfei Liang, Yui Chun S. Wan, Kuai Yu, H. Criss Hartzell, Huanghe Yang
Niclosamide, a proposed TMEM16A inhibitor for asthma and COPD, unexpectedly enhances TMEM16A activity, raising caution for its clinical use. Discovering its binding site on TMEM16A aids in developing targeted modulators for various diseases.
Article
Vamseedhar Rayaprolu, Heini M. Miettinen, William D. Baker, Victoria C. Young, Matthew Fisher, Gwendolyn Mueller, William O. Rankin, John T. Kelley, William J. Ratzan, Lee Min Leong, Joshua A. Davisson, Bradley J. Baker, Susy C. Kohout
Rayaprolu et al. investigated how hydrophobic residues impact the function of the voltage-sensing phosphatase. They mutated different positions in the S1 helix of the voltage-sensing domain and found more energy was needed for enzyme activation while less was needed to move the sensor.
Article
Sebastian Duno-Miranda, Shane R. Nelson, David V. Rasicci, Skylar M.L. Bodt, Joseph A. Cirilo, Jr, Duha Vang, Sivaraj Sivaramakrishnan, Christopher M. Yengo, David M. Warshaw
Duno-Miranda et al. investigate the E525K mutation in human β-cardiac myosin, a protein crucial for heart contraction, and its role in causing dilated cardiomyopathy (DCM). They demonstrate that the length of the myosin tail influences its self-inhibition and that the E525K mutation strengthens this effect, potentially reducing heart contractility in DCM.
Article
Noel Tewes, Beatrice Kubitzki, Flandrit Bytyqi, Nikola Metko, Sebastian Mach, Gerhard Thiel, Oliver Rauh
Tewes et al. use a simple K+ channel pore to examine filter gating. Voltage-dependent closings in pore-helix mutants can be explained by an elevated sensitivity to block by trace contaminations of Ba2+. This means that the dwell time of ions in the filter determines the closed times of the filter gate.
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Current Issue
Volume 156,
Issue 6,
3 June 2024
Reviews & Opinions
Research News
Ben Short
JGP study shows that hydrophobic residues in the S1 transmembrane domain modulate the voltage-sensor movements and enzymatic activity of voltage-sensing phosphatase.
Viewpoint
Jeffrey R. Holt, Robert Fettiplace, Ulrich Müller
In this Viewpoint, Holt, Fettiplace, and Müller weigh the evidence supporting a role for PIEZO and TMC channels in mechanosensory transduction in inner ear hair cells.
Research News
Ben Short
JGP study shows that a mutation linked to dilated cardiomyopathy stabilizes β-cardiac myosin in its autoinhibited, super-relaxed state.

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