Issues

JGP study reveals that oxidative stress can induce stable posttranslational modifications of RyR1 that increase the channel’s open probability and could therefore disrupt muscle contractility.

After decades of obscurity, we are finally gaining mechanistic insight into the function of myosin-binding protein-H in skeletal muscle regulation.

Myosin-binding protein H (MyBP-H) is an understudied paralog of the muscle regulator myosin-binding protein C (MyBP-C). Mead et al. reveal that MyBP-H is highly expressed in the muscles of prenatal rats and larval zebrafish and that MyBP-H impacts sarcomere function despite lacking key regulatory domains.

Ca²⁺ release via the ryanodine receptor 1 (RyR1) is essential for skeletal muscle contraction. Here, Steinz et al. combine targeted mass spectrometry and single-channel recordings to elucidate how the stable oxidative posttranslational modifications 3-nitrotyrosine (3-NT) and malondialdehyde adducts (MDA) affect RyR1 channel gating.

Hi1a, a bilobed peptide isolated from spider venom, reduces ischemic cell death by inhibiting ASIC1a channels. Berger and MacLean show that each domain of Hi1a binds to the same site on ASIC1a subunits, accounting for this peptide’s unusual functional effects.

Bacterial TAXI-TRAP transporters are widespread but poorly understood. Davies et al. characterize a TAXI from Vibrio cholerae, revealing its glutamate specificity, binding determinants, and unusual membrane component. As glutamate is a key metabolite in pathogens, glutamate transporters are potential therapeutic targets.

The mechanically gated ion channel Piezo2 initiates signaling molecule release in gastrointestinal epithelial mechanoreceptors. Mercado-Perez et al. demonstrate that some Piezo2 clusters in these cells interact with E-cadherin and actin cytoskeleton at the lateral wall.

The activation of DRP1 during ischemia-reperfusion results in mitochondrial fragmentation, which is known to be a key trigger of cardiac injuries. Dubois et al. evaluate whether preconditioning with exercise training can limit the activation of DRP1 and excessive mitochondrial fragmentation during myocardial ischemia-reperfusion.

Murthy and Baker propose a stochastic two-state thermodynamic model of muscle contraction that provides a novel interpretation of muscle mechanics and chemistry, in which the entropy of an ensemble of molecules contributes to the energetics and mechanics of the contractile system.