Gating Of Trpv5 Channel Activity By Phosphorylation And Exogenous Ligands

The transient receptor potential vanilloid 5 (TRPV5) channel belongs to the transient receptor potential (TRP) channel family. While other members of the six subfamilies (TRPV, TRPC, TRPM, TRPA, TRPP, and TRPML) are mainly non-selective cation channels, two members of the TRPV subfamily (TRPV5 and TRPV6) are highly Ca2+ selective. TRPV5 and is primarily expressed on the apical membrane of the distal convoluted tubule in the kidney and plays an important role in systemic Ca2+ homeostasis. One important regulator of TRPV5 found in multiple studies is protein kinase A (PKA), which activates the channel by phosphorylating T709. Synthetic compounds can also interact with TRPV5. Through the use of cryo-electron microscopy (cryo-EM), we have been able to gain structural insight on the mechanisms of TRPV5 modulation by both exogenous and endogenous factors. Here we present proposed mechanisms for activation of TRPV5 by PKA and inhibition of TRPV5 by synthetic compounds.