Inhibition of TRPP3 by calmodulin through Ca2+/calmodulin-dependent protein kinase II

Transient receptor potential (TRP) polycystin-3 (TRPP3) is a non-selective cation channel activated by Ca2+ and protons and is involved in regulating ciliary Ca2+ concentration, hedgehog signaling and sour tasting. The TRPP3 channel function and regulation are still not well understood. Here we investigated regulation of TRPP3 by calmodulin (CaM) by means of electrophysiology and Xenopus oocytes as an expression model. We found that TRPP3 channel function is enhanced by calmidazolium, a CaM antagonist, and inhibited by CaM through binding of the CaM N-lobe to a TRPP3 C-terminal domain not overlapped with the EF-hand. We further revealed that the TRPP3/CaM interaction promotes phosphorylation of TRPP3 at threonine 591 by Ca2+/CaM-dependent protein kinase II, which mediates the inhibition of TRPP3 by CaM.