Thermosensory and Nonthermosensory Isoforms of Drosophila melanogaster TRPA1 Reveal Heat-Sensor Domains of a ThermoTRP Channel

Lixian Zhong, Andrew Bellemer, Haidun Yan, Ken Honjo, Jessica Robertson, Richard Y. Hwang, Geoffrey S. Pitt, W. Daniel Tracey

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

Specialized somatosensory neurons detect temperatures ranging from pleasantly cool or warm to burning hot and painful (nociceptive). The precise temperature ranges sensed by thermally sensitive neurons is determined by tissue-specific expression of ion channels of the transient receptor potential (TRP) family. We show here that in Drosophila, TRPA1 is required for the sensing of nociceptive heat. We identify two previously unidentified protein isoforms of dTRPA1, named dTRPA1-C and dTRPA1-D, that explain this requirement. A dTRPA1-C/D reporter was exclusively expressed in nociceptors, and dTRPA1-C rescued thermal nociception phenotypes when restored to mutant nociceptors. However, surprisingly, we find that dTRPA1-C is not a direct heat sensor. Alternative splicing generates at least four isoforms of dTRPA1. Our analysis of these isoforms reveals a 37-amino-acid-long intracellular region (encoded by a single exon) that is critical for dTRPA1 temperature responses. The identification of these amino acids opens the door to a biophysical understanding of a molecular thermosensor.

Original languageEnglish (US)
Pages (from-to)43-55
Number of pages13
JournalCell Reports
Volume1
Issue number1
DOIs
StatePublished - Jan 26 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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