Journal
CELL
Volume 178, Issue 6, Pages 1375-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2019.07.034
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Funding
- NIA T32 training grant
- MOST [2018YFA0507003, 31420103909, 81872945, 81720108031]
- NSFC [2018YFA0507003, 31420103909, 81872945, 81720108031]
- 111 project of the MOE [B08029]
- National Research Foundation of Korea [NRF-2017R1A4A1015564]
- NINDS
- NIGMS
- NIA
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In search of the molecular identities of cold-sensing receptors, we carried out an unbiased genetic screen for cold-sensing mutants in C. elegans and isolated a mutant allele of glr-3 gene that encodes a kainate-type glutamate receptor. While glutamate receptors are best known to transmit chemical synaptic signals in the CNS, we show that GLR-3 senses cold in the peripheral sensory neuron ASER to trigger cold-avoidance behavior. GLR-3 transmits cold signals via G protein signaling independently of its glutamate-gated channel function, suggesting GLR-3 as a metabotropic cold receptor. The vertebrate GLR-3 homolog GluK2 from zebrafish, mouse, and human can all function as a cold receptor in heterologous systems. Mouse DRG sensory neurons ex- prc GluK2, and GluK2 knockdown in these neurons suppresses their sensitivity to cold but not cool temperatures. Our study identifies an evolutionarily conserved cold receptor, revealing that a central chemical receptor unexpectedly functions as a thermal receptor in the periphery.
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