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      Polymodal Nociception in Drosophila Requires Alternative Splicing of TrpA1

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      Current Biology

      Elsevier BV

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          Abstract

          <p id="P3">Transcripts of noxious stimulus-detecting TrpA1 channels are alternatively spliced. Despite the importance of nociception for survival, the <i>in vivo</i> significance of expressing different <i>TrpA1</i> isoforms is largely unknown. Here we develop a novel genetic approach to generate <i>Drosophila</i> knock-in strains expressing single TrpA1 isoforms. <i>Drosophila</i> TrpA1 mediates heat and UVC-triggered nociception. We show 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 knock-in flies reveals the striking functional specificity; TrpA1-C mediates UVC-nociception, whereas TrpA1-D mediates heat-nociception. Therefore, <i>in vivo</i> functions of TrpA1-C and TrpA1-D are different from each other, and are different from their <i>in vitro</i> properties. Our results indicate that a given sensory stimulus preferentially activates a single TrpA1 isoform <i>in vivo</i>, and that polymodal nociception requires co-expression of TrpA1 isoforms, providing novel insights of how alternative splicing regulates nociception. </p><p id="P4">Gu <i>et al</i>. demonstrate that heat and UVC light preferentially activate distinct <i>Drosophila</i> TrpA1 isoforms <i>in vivo</i>, and polymodal nociception requires co-expression of TrpA1-C and TrpA1-D. </p>

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          Author and article information

          Journal
          Current Biology
          Current Biology
          Elsevier BV
          09609822
          November 2019
          November 2019
          Article
          10.1016/j.cub.2019.09.070
          6938258
          31735672
          © 2019

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