Editors' ChoicePhysiology

Coming out of the cold

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Science Signaling  17 Sep 2019:
Vol. 12, Issue 599, eaaz4967
DOI: 10.1126/scisignal.aaz4967

A glutamate receptor acts as a cold sensor through a channel-independent, G protein–dependent mechanism.

The ability to detect and respond to cold temperatures is an evolutionarily conserved necessity for survival. Gong et al. identified the kainate-type glutamate receptor GLR-3 as a sensor for cold temperatures in Caenorhabditis elegans through a screen using the epithelial intestinal cells of this organism, which show Ca2+ responses in response to cooling. These responses were induced in Chinese hamster ovary (CHO) cells by ectopic expression of GLR-3 or the zebrafish or human homologs. GLR-3 was present not only in intestinal epithelial cells, but also in the sensory neuron ASER. C. elegans that were deficient in glr-3 did not show Ca2+ responses to cooling, a defect that was rescued by expression of GLR-3 or the mouse homolog GluK2. In addition, glr-3 mutant worms did not exhibit avoidance behaviors to cold, which was rescued by expression of glr-3 or GluK2 specifically in the ASER neuron. Unlike GluK2, GLR-3 did not show channel activity when expressed in cells. However, the cold sensitivity defects of glr-3 mutants were rescued by expression of channel-dead GluK2 mutants or GLR-3 with analogous mutations in the ASER neuron. Furthermore, C. elegans mutants lacking glutamate signaling retained cold sensitivity. These results indicate that cold sensing by GLR-3 was independent of glutamate binding or channel activity. Pharmacological and genetic analyses indicated that GLR-3 coupling to Gi/o proteins was required for cold-induced Ca2+ responses. Thus, an evolutionarily conserved glutamate receptor acts as a cold sensor through a channel-independent, G protein–dependent mechanism.

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