• Top page
  • Timetable
  • Per session
  • Per presentation
  • How to
  • Meeting Planner




開催日 2014/9/11
時間 10:00 - 11:00
会場 Room J(313+314)
Chairperson(s) 中川 貴之 / Takayuki Nakagawa (京都大学医学部附属病院 薬剤部 / Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Japan)
鈴木 えみ子 / Emiko Suzuki (国立遺伝学研究所 構造遺伝学研究センター / Structural biology Center, National Institute of Genetics, Japan)

The ubiquitin proteasome system negatively regulates BMP signaling to inhibit nociceptors in Drosophila

  • O1-J-2-2
  • 本庄 賢 / Ken Honjo:1 鈴木 えみ子 / Emiko Suzuki:1 Tracey Dan / Dan Tracey:2 
  • 1:国立遺伝学研究所 / National Institute of Genetics, Japan 2:Department of Anesthesiology, Cell Biology, Neurobiology, Duke University Medical Center, Durham, USA / Department of Anesthesiology, Cell Biology, Neurobiology, Duke University Medical Center, Durham, USA 

A comprehensive understanding of the molecular machinery of nociception is essential to improve the treatment of pain. Nociceptors are specialized sensory neurons to sense potentially tissue-damaging noxious stimuli. Since hypersensitivity of nociceptors can cause pathological states such as neuropathic pain, the molecular machinery controlling the sensitivity of nociceptors has been extensively investigated. However, our understanding of the molecular mechanisms controlling the sensitivity of nociceptors is far from complete.
Drosophila is an emerging attractive system to study the molecular basis of nociception. Using this model, we show that the BMP signaling pathway is under the control of the ubiquitin proteasome system (UPS) as a regulator of nociception. Through a nociceptor-specific RNAi screen, we isolated candidate nociception genes including the E3 ubiquitin ligase highwire (hiw) and the proteasome alpha1 subunit (prosα1). Further analyses of UPS components revealed that the UPS function in nociceptors is responsible for both positive and negative regulations of nociception. Mutation of hiw and prosα1 knockdown each impaired thermosensory function but simultaneously sensitized a transduction-independent function of nociceptors. We found that the sensitization pathway is associated with BMP signaling: BMP signaling in nociceptors was down-regulated by a ubiquitylation-dependent mechanism and acute activation of BMP signaling in nociceptors was sufficient to sensitize nociception without altering nociceptor morphology. We also found that tissue damage both induced larval hyperalgesia and activated BMP signaling. We thus propose that the Hiw-UPS pathway negatively regulates a BMP pathway that normally functions to sensitize nociceptors following tissue damage.

Copyright © Neuroscience2014. All Right Reserved.