Transient receptor potential channels articles from across Nature Portfolio

Both PKC phosphorylation and elevated calcium levels are required for TRPM5 activation, the phosphorylation is crucial for channel-evoked currents at physiological membrane potentials.

Long-chain acyl-Coenzyme-A is a metabolic intermediate with important signaling functions. Here the authors show that it activates the Ca²⁺ selective ion channels TRPV5 and TRPV6 and elucidate the structural basis of TRPV5 activation using CryoEM.

Neuberger et al. report the structure of human channel TRPV6 in complex with a cannabinoid inhibitor tetrahydrocannabivarin (THCV) and explore the pathway taken by the drug to reach binding sites in the portals that connect the membrane environment to the central cavity of the ion channel pore.

An integrated structural biology approach uncovers the structural complexity of the intrinsically disordered region (IDR) within the TRPV4 ion channel. Multiple stimulatory and inhibitory elements were identified within the IDR that modulate channel activity in a lipid-dependent manner.

Despite TRPV4’s medical importance, the mechanisms of ligand-mediated channel gating and its regulation by Rho GTPase are unclear. Here, the authors report the structures of TRPV4 in complex with RhoA and ligands, offering atomic-level insights into their functions.

Nadezhdin et al. present structures of human TRPV4 in complex with the GTPase RhoA, in the apo, agonist 4α-PDD and antagonist HC-067047 bound states, uncovering the mechanisms of channel activation, inhibition and disease-causing mutations.

The polycystin complex structure has been solved at near-atomic resolution. Its surprising architecture provides new insights into the transient receptor potential (TRP) family of cation channels and the pathogenesis of autosomal dominant polycystic kidney disease. This discovery should have a transformative impact on the development of treatment strategies to cure the disease.