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

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 i...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2011-11, Vol.108 (46), p.E1184-E1191
Main Authors: Cordero-Morales, Julio F, Gracheva, Elena O, Julius, David
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
calcium
Crotalus
Cytoplasm
Cytoplasm - metabolism
detectors
Dimerization
Drosophila
Drosophila melanogaster
Drosophila Proteins - chemistry
Drosophila Proteins - metabolism
Electrophysiology - methods
evolution
heat
Hot Temperature
Humans
invertebrates
mammals
Neurons
Oocytes - metabolism
Physiology
PNAS Plus
Point Mutation
Protein Structure, Tertiary
Proteins
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - metabolism
RNA, Complementary - metabolism
sensory neurons
Snakes
Transient Receptor Potential Channels - chemistry
Transient Receptor Potential Channels - metabolism
TRPA1 Cation Channel
TRPC Cation Channels - chemistry
TRPC Cation Channels - metabolism
Xenopus
Xenopus laevis - metabolism
Zebrafish
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1114124108