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Curr Biol. 2019 Dec 2;29(23):3961-3973.e6. doi: 10.1016/j.cub.2019.09.070. Epub 2019 Nov 14.

Polymodal Nociception in Drosophila Requires Alternative Splicing of TrpA1.

Author information

1
Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
2
Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: yang.xiang@umassmed.edu.

Abstract

Transcripts of noxious stimulus-detecting TrpA1 channels are alternatively spliced. Despite the importance of nociception for survival, the in vivo significance of expressing different TrpA1 isoforms is largely unknown. Here, we develop a novel genetic approach to generate Drosophila knockin strains expressing single TrpA1 isoforms. Drosophila TrpA1 mediates heat and UVC-triggered nociception. We show that TrpA1-C and TrpA1-D, two alternative isoforms, are co-expressed in nociceptors. When examined in heterologous cells, both TrpA1-C and TrpA1-D are activated by heat and UVC. By contrast, analysis of knockin flies reveals the striking functional specificity; TrpA1-C mediates UVC-nociception, whereas TrpA1-D mediates heat-nociception. Therefore, in vivo functions of TrpA1-C and TrpA1-D are different from each other and are different from their in vitro properties. Our results indicate that a given sensory stimulus preferentially activates a single TrpA1 isoform in vivo and that polymodal nociception requires co-expression of TrpA1 isoforms, providing novel insights of how alternative splicing regulates nociception.

KEYWORDS:

Drosophila; TrpA1; alternative splicing; genome engineering; nociception; polymodal nociceptors; thermogenetics; transient receptor potential; translational reporters

PMID:
31735672
DOI:
10.1016/j.cub.2019.09.070

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