Members of the rusc protein family interact with Sufu and inhibit vertebrate hedgehog signaling

Zhigang Jin, Tyler Schwend, Jia Fu, Zehua Bao, Jing Liang, Huimin Zhao, Wenyan Mei, Jing Yang

Research output: Contribution to journalArticle

Abstract

Hedgehog (Hh) signaling is fundamentally important for development and adult tissue homeostasis. It is well established that in vertebrates Sufu directly binds and inhibits Gli proteins, the downstream mediators of Hh signaling. However, it is unclear how the inhibitory function of Sufu towards Gli is regulated. Here we report that the Rusc family of proteins, the biological functions of which are poorly understood, form a heterotrimeric complex with Sufu and Gli. Upon Hh signaling, Rusc is displaced from this complex, followed by dissociation of Gli from Sufu. In mammalian fibroblast cells, knockdown of Rusc2 potentiates Hh signaling by accelerating signaling-induced dissociation of the Sufu-Gli protein complexes. In Xenopus embryos, knockdown of Rusc1 or overexpression of a dominant-negative Rusc enhances Hh signaling during eye development, leading to severe eye defects. Our study thus uncovers a novel regulatory mechanism controlling the response of cells to Hh signaling in vertebrates.

Original languageEnglish (US)
Pages (from-to)3944-3955
Number of pages12
JournalDevelopment (Cambridge)
Volume143
Issue number21
DOIs
StatePublished - Nov 1 2016

Keywords

  • Gli
  • Hedgehog signaling
  • Human
  • Mouse
  • Rusc
  • Sufu
  • Xenopus

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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