Calcium transport and sensing in TRPC channels - New insights into a complex feedback regulation.

Canonical TRP (TRPC) channels are a still enigmatic family of signaling molecules with multimodal sensing features. These channels enable Ca influx through the plasma membrane to control a diverse range of cellular functions. Based on both regulatory- and recently uncovered structural features, TRPC channels are considered to coordinate Ca and other divalent cations not only within the permeation path but also at additional sensory sites. Analysis of TRPC structures by cryo-EM identified multiple regulatory ion binding pockets. With this review, we aim at an overview and a critical discussion of the current concepts of divalent sensing by TRPC channels.