- Kir6.1 in islet KATP channels
Kir6.2-containing KATP channels are prominent in pancreatic β cells, and gain-of-function mutations in these channels are the most common cause of human neonatal diabetes mellitus. Remedi et al. find that Kir6.1 subunits are also present in pancreatic KATP channels and that gain-of-function mutations can also cause impaired glucose tolerance and insulin secretion.
- Binding curves and parameter identifiability
In their preceding paper, Middendorf and Aldrich describe a method to determine the accuracy of binding parameters estimated from models of agonist binding. Here, they present an approach to determine whether binding parameters can be accurately estimated from experimental, or noisy, data.
- Vesicle recycling in stellate astrocytic processes
Communication between astrocytes and neurons has been difficult to study because cultured astrocytes do not resemble those in vivo. Wolfes et al. develop a stellate astrocyte monoculture with physiological characteristics and find that VAMP2 and SYT7 mark distinct vesicle populations in astrocytes.
- AChR gating
Gupta et al. use single-channel electrophysiology to investigate the gating mechanism of acetylcholine receptor ion channels. They propose that channel opening starts at the M2–M3 linker and ligand-binding sites and proceeds through four brief intermediate conformations before ending with the collapse of a gate bubble.
- Structural identifiability of binding parameters
Precise mathematical descriptions of ligand–protein interactions are hindered by the inability to experimentally measure affinity and cooperativity, although these parameters can be estimated from agonist binding models. Middendorf and Aldrich present a method to determine the accuracy of parameters estimated in this way.
- Disrupted muscle maturation in Huntington’s disease
The R6/2 mouse model of Huntington’s disease exhibits reduced skeletal muscle ClC-1 currents. Miranda et al. investigate early stages of disease in these mice and find an early and progressive disruption of ClC-1 as well as altered muscle maturation based on myosin heavy chain isoform expression.
- Modeling convective flow in brain parenchyma
A “glymphatic mechanism” has been proposed to mediate convective fluid transport from para-arterial to paravenous extracellular space in the brain. Jin et al. model such a system and find that diffusion, rather than convection, can account for the transport of solutes.
- Structure and mechanism of the ATP synthase rotor
The ATP synthase is a molecular rotor that recycles ADP into ATP. Leone and Faraldo-Gómez use structural modeling to reinterpret and reconcile recent cryo-EM data for its membrane domain with other experimental evidence, gaining insights into its mechanism and the mode of inhibition by oligomycin.