- 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.
- 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.
- Interfilament binding of tethered molecules
Models of cellular contraction, for example, in striated muscle, usually involve mass action kinetics. Mijailovich et al. implement spatially explicit actomyosin interactions in the Monte Carlo platform MUSICO and show the extent to which myosin tethering affects other biological parameters.
- Independent activation of TMEM16A subunits
The TMEM16 family contains dimeric membrane proteins activated by intracellular Ca2+. Realizing that lipid scramblase family members contain two independently activated subunits, Lim et al. use concatenated TMEM16A subunits to show that ion channel members contain two independently activated pores.
- Separate activation of TMEM16A subunits
TMEM16 lipid scramblases are formed from two identical subunits, but the pore architecture of TMEM16 channels remains unclear. Jeng et al. use tandem dimers of TMEM16A subunits with different mutations and show that each subunit comprises an independent pore and contains more than one Ca2+-binding site.