An intracellular activation of Smoothened that is independent of Hedgehog stimulation in Drosophila

Kai Jiang, Yajuan Liu, Jie Zhang, Jianhang Jia

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Smoothened (Smo), a GPCR family protein, plays a critical role in the reception and transduction of Hedgehog (Hh) signal. Smo is phosphorylated and activated on the cell surface; however, it is unknown whether Smo can be intracellularly activated. Here, we demonstrate that inactivation of the ESCRT-III causes dramatic accumulation of Smo in the ESCRT-III/MVB compartment, and subsequent activation of Hh signaling. In contrast, inactivation of ESCRTs 0-II induces mild Smo accumulation in the ESCRT-III/MVB compartment. We provide evidence that Kurtz (Krz), the Drosophila ß- arrestin2, acts in parallel with the ESCRTs 0-II pathway to sort Smo to the multivesicular bodies and lysosome-mediated degradation. Additionally, upon inactivation of ESCRT-III, all active and inactive forms of Smo are accumulated. Endogenous Smo accumulated upon ESCRT-III inactivation is highly activated, which is induced by phosphorylation but not sumoylation. Taken together, our findings demonstrate a model for intracellular activation of Smo, raising the possibility for tissue overgrowth caused by an excessive amount, rather than mutation of Smo.

Original languageEnglish
Article numberjcs.211367
JournalJournal of Cell Science
Volume131
Issue number1
DOIs
StatePublished - Jan 1 2018

Bibliographical note

Publisher Copyright:
© 2018. Published by The Company of Biologists Ltd.

Keywords

  • ESCRT
  • Hh
  • Signal transduction
  • Smo
  • Vps20
  • Vps32

ASJC Scopus subject areas

  • Cell Biology

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