Title

Polymodal Nociception in Drosophila Requires Alternative Splicing of TrpA1

UMMS Affiliation

Department of Neurobiology; Freeman Lab; Yang Xiang Lab; Graduate School of Biomedical Sciences

Publication Date

2019-12-02

Document Type

Article

Disciplines

Genomics | Neuroscience and Neurobiology

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

DOI of Published Version

10.1016/j.cub.2019.09.070

Source

Curr Biol. 2019 Dec 2;29(23):3961-3973.e6. doi: 10.1016/j.cub.2019.09.070. Epub 2019 Nov 14. Link to article on publisher's site

Journal/Book/Conference Title

Current biology : CB

Related Resources

Link to Article in PubMed

PubMed ID

31735672

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