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ON THE COVER
TPC3 has a dimeric structure of a two domain–type subunit. Each domain has a respective role. Domain I (aqua) serves as the binding site for PI(3,4)P2 (sphere model), while domain II (purple) plays a chief role in voltage sensing by the arginine residues in the S4 helix (red cylinders). The authors found that the PI(3,4)P2 binding in domain I is coupled with the voltage sensing in domain II by the interaction between the pore-lining S6 in two domains (stick model). See page 986. - PDF Icon PDF LinkTable of Contents
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In Memoriam
In Memoriam: David C. Gadsby, PhD
Andersen et al. commemorate the life of the eminent physiologist, David Gadsby.
Research News
How dendritic spines shape calcium dynamics
JGP study develops mathematical model that describes how calcium signaling could be influenced by spine geometry and ultrastructure.
Commentary
With PIPs, you get ZIPs and blips
Senning discusses new research on the regulation of two-pore sodium channels by different phosphoinositide phosphates.
Tutorials
A primer on resolving the nanoscale structure of the plasma membrane with light and electron microscopy
Taraska reviews the imaging methods that are being used to understand the structure of the plasma membrane at the molecular level.
Research Articles
Phosphoinositides modulate the voltage dependence of two-pore channel 3
Among the three two-pore channels (TPCs), TPC1 and TPC2 are selectively activated by PI(3,5)P2, while TPC3 has been considered not to respond to any PIP2s. Shimomura and Kubo find that TPC3 responds to both PI(3,5)P2 and PI(3,4)P2, but not to PI(4,5)P2.
Myosin lever arm orientation in muscle determined with high angular resolution using bifunctional spin labels
High-resolution structural information is invaluable for understanding muscle function. Savich et al. use bifunctional spin labeling to determine the orientation of the myosin lever arm in muscle fibers at high resolution under ambient conditions, augmenting previous insights obtained from fluorescence and EM.
Dendritic spine geometry and spine apparatus organization govern the spatiotemporal dynamics of calcium
Dendritic spines can have numerous different shapes, but how this affects the function of these neuronal subcompartments is unclear. Bell et al. develop a mathematical model that reveals how the size and shape of both the spine head and spine apparatus impact local calcium dynamics.
A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2
Erdem et al. compare the kinetics of the SLC6 family glycine transporters GlyT1 and GlyT2. Though the two transporters are rate-limited by distinct reaction steps, they both display high transport capacity, with the kinetics of GlyT1 sufficient to supply extracellular glycine to the NMDA receptor.
Communications
Regulation of heart rate and the pacemaker current by phosphoinositide 3-kinase signaling
Heart rate is set by the specialized tissue of the sinoatrial node. Lin et al. demonstrate a novel role for phosphoinositide 3-kinase in regulating cardiac pacemaking currents independently of the autonomic nervous system, a finding with relevance for diabetes, heart disease, and cancer.
