Heterotrimeric Gi Proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migration

Authors
Polizio, Ariel Héctor; Chinchilla, Pilar; Chen, Xiaole; Kim, Sangbumn; Manning, David R.; Riobo, Natalia A.
Publication Year
2011
Language
English
Format
article
Status
Published version
Description
Evidence supporting the functionality of Smoothened (SMO), an essential transducer in most pathways engaged by Hedgehog (Hh), as a Gi-coupled receptor contrasts with the lack of an apparently consistent requirement for Gi in Hh signal transduction. In the present study, we sought to evaluate the role of SMO-Gi coupling in fibroblast migration induced by Sonic Hedgehog (Shh). Our results demonstrate an absolute requirement for Gi in Shh-induced fibroblast migration. We found that Shh acutely stimulates the small Rho GTPases Rac1 and RhoA via SMO through a Gi protein- and PI3K-dependent mechanism, and that these are required for cell migration. These responses were independent of transcription by Gli and of the C-terminal domain of SMO, as we show using a combination of molecular and genetic tools. Our findings provide a mechanistic model for fibroblast migration in response to Shh and underscore the role of SMO-Gi coupling in non-canonical Hh signaling.
Fil: Polizio, Ariel Héctor. Thomas Jefferson University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Chinchilla, Pilar. Thomas Jefferson University; Estados Unidos
Fil: Chen, Xiaole. Thomas Jefferson University; Estados Unidos
Fil: Kim, Sangbumn. Thomas Jefferson University; Estados Unidos
Fil: Manning, David R.. University Of Pennsylvania; Estados Unidos
Fil: Riobo, Natalia A.. Thomas Jefferson University; Estados Unidos
Subject
Sonic HEDGEHOG
migration
cancer
signal pathways
Bioquímica y Biología Molecular
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Open access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/13181