Cold sensory transduction through the STIM-Orai signaling pathway

The STIM-Orai signaling pathway mediates Ca²⁺ signals vital for controlling transcription and cell growth. The Ca²⁺ sensing STIM proteins are activated by depletion of Ca²⁺ stored in the ER, and translocate into ER-PM junctions to gate PM Orai channels. STIM1 activation also results from heating STIM1 proteins, and new evidence reveals the STIM1-mediated gating of Orai1 channels is activated by noxious cooling of cells. This activation of the STIM-Orai pathway may be important in mediating vascular dilation that occurs in response to severe cold exposure.