Cytoplasmic ankyrin repeats of transient receptor potential A1 (TRPA1) dictate sensitivity to thermal and chemical stimuli

Julio Cordero-Morales, Elena O. Gracheva, David Julius

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Transient receptor potential (TRP) channels are polymodal signal detectors that respond to a wide array of physical and chemical stimuli, making them important components of sensory systems in both vertebrate and invertebrate organisms. Mammalian TRPA1 channels are activated by chemically reactive irritants, whereas snake and Drosophila TRPA1 orthologs are preferentially activated by heat. By comparing human and rattlesnake TRPA1 channels, we have identified two portable heat-sensitive modules within the ankyrin repeat-rich aminoterminal cytoplasmic domain of the snake ortholog. Chimeric channel studies further demonstrate that sensitivity to chemical stimuli and modulation by intracellular calcium also localize to the N-terminal ankyrin repeat-rich domain, identifying this region as an integrator of diverse physiological signals that regulate sensory neuron excitability. These findings provide a framework for understanding how restricted changes in TRPA1 sequence account for evolution of physiologically diverse channels, also identifying portable modules that specify thermosensitivity.

Original languageEnglish (US)
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number46
DOIs
StatePublished - Nov 15 2011

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Ankyrin Repeat
Transient Receptor Potential Channels
Snakes
Hot Temperature
Crotalus
Terminal Repeat Sequences
Irritants
Sensory Receptor Cells
Invertebrates
Drosophila
Vertebrates
Calcium

All Science Journal Classification (ASJC) codes

  • General

Cite this

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