Members of the Rusc Protein Family Interact with Sufu and Inhibit Vertebrate Hedgehog Signaling

Overview

Journal Development

Specialty Biology

Date 2016 Sep 17

PMID 27633991

Citations 6

Authors

Zhigang Jin

Tyler Schwend

Jia Fu

Zehua Bao

Jing Liang

Huimin Zhao

Wenyan Mei

Jing Yang

Affiliations

Soon will be listed here.

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.

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