Thermosensory and Nonthermosensory Isoforms of Drosophila Melanogaster TRPA1 Reveal Heat-sensor Domains of a ThermoTRP Channel

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2012 Feb 21

PMID 22347718

Citations 125

Authors

Lixian Zhong

Andrew Bellemer

Haidun Yan

Honjo Ken

Robertson Jessica

Richard Y Hwang

Geoffrey S Pitt

W Daniel Tracey

Affiliations

Soon will be listed here.

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.

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