Major vacuolar TPC1 channel in stress signaling: what matters, K + , Ca 2+ conductance or an ion-flux independent mechanism?

Two-pore cation channel, TPC1, is ubiquitous in the vacuolar membrane of terrestrial plants and mediates the long distance signaling upon biotic and abiotic stresses. It possesses a wide pore, which transports small mono- and divalent cations. K + is transported more than 10-fold faster than Ca 2+ , which binds with a higher affinity within the pore. Key pore residues, responsible for Ca 2+ binding, have been recently identified. There is also a substantial progress in the mechanistic and structural understanding of the plant TPC1 gating by membrane voltage and cytosolic and luminal Ca 2+ . Collectively, these gating factors at resting conditions strongly reduce the potentially lethal Ca 2+ leak from the vacuole. Such tight control is impressive, bearing in mind high unitary conductance of the TPC1 and its abundance, with thousands of active channel copies per vacuole. But it remains a mystery how this high threshold is overcome upon signaling, and what type of signal is emitted by TPC1, whether it is Ca 2+ or electrical one, or a transduction via protein conformational change, independent on ion conductance. Here we discuss non-exclusive scenarios for the TPC1 integration into Ca 2+ , ROS and electrical signaling.