Wnt signalling antagonizes stress granule assembly through a Dishevelled-dependent mechanism

Cells often respond to diverse environmental stresses by inducing stress granules (SGs) as an adaptive mechanism. SGs are generally assembled as a result of aggregation of mRNAs stalled in a translational pre-initiation complex, mediated by a set of RNA-binding proteins such as G3BP and TIA-1. SGs m...

Full description

Bibliographic Details
Main Authors:	Sahoo, Pabitra K., Murawala, Prayag, Sawale, Pravin T., Sahoo, Manas R., Tripathi, Mukesh M., Gaikwad, Swati R., Seshadri, Vasudevan, Joseph, Jomon
Format:	Online
Language:	English
Published:	The Company of Biologists 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507204/

id	pubmed-3507204
recordtype	oai_dc
spelling	pubmed-35072042012-12-04 Wnt signalling antagonizes stress granule assembly through a Dishevelled-dependent mechanism Sahoo, Pabitra K. Murawala, Prayag Sawale, Pravin T. Sahoo, Manas R. Tripathi, Mukesh M. Gaikwad, Swati R. Seshadri, Vasudevan Joseph, Jomon Research Article Cells often respond to diverse environmental stresses by inducing stress granules (SGs) as an adaptive mechanism. SGs are generally assembled as a result of aggregation of mRNAs stalled in a translational pre-initiation complex, mediated by a set of RNA-binding proteins such as G3BP and TIA-1. SGs may serve as triage centres for storage, translation re-initiation or degradation of specific mRNAs. However, the mechanism involved in the modulation of their assembly/disassembly is unclear. Here we report that Wnt signalling negatively regulates SG assembly through Dishevelled (Dvl), a cytoplasmic Wnt effector. Overexpression of Dvl2, an isoform of Dvl, leads to impairment of SG assembly through a DEP domain dependent mechanism. Intriguingly, the Dvl2 mutant K446M, which corresponds to an analogous mutation in Drosophila Dishevelled DEP domain (dsh1) that results in defective PCP pathway, fails to antagonize SG assembly. Furthermore, we show that Dvl2 exerts the antagonistic effect on SG assembly through a mechanism involving Rac1-mediated inhibition of RhoA. Dvl2 interacts with G3BP, a downstream component of Ras signalling involved in SG assembly, and functional analysis suggests a model wherein the Dvl-Rac1-RhoA axis regulates G3BP's SG-nucleating activity. Collectively, these results define an antagonistic effect of Wnt signalling on SG assembly, and reveal a novel role for Wnt/Dvl pathway in the modulation of mRNA functions. The Company of Biologists 2011-11-18 /pmc/articles/PMC3507204/ /pubmed/23213403 http://dx.doi.org/10.1242/bio.2011023 Text en © 2011. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by-nc-sa/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Sahoo, Pabitra K. Murawala, Prayag Sawale, Pravin T. Sahoo, Manas R. Tripathi, Mukesh M. Gaikwad, Swati R. Seshadri, Vasudevan Joseph, Jomon
spellingShingle	Sahoo, Pabitra K. Murawala, Prayag Sawale, Pravin T. Sahoo, Manas R. Tripathi, Mukesh M. Gaikwad, Swati R. Seshadri, Vasudevan Joseph, Jomon Wnt signalling antagonizes stress granule assembly through a Dishevelled-dependent mechanism
author_facet	Sahoo, Pabitra K. Murawala, Prayag Sawale, Pravin T. Sahoo, Manas R. Tripathi, Mukesh M. Gaikwad, Swati R. Seshadri, Vasudevan Joseph, Jomon
author_sort	Sahoo, Pabitra K.
title	Wnt signalling antagonizes stress granule assembly through a Dishevelled-dependent mechanism
title_short	Wnt signalling antagonizes stress granule assembly through a Dishevelled-dependent mechanism
title_full	Wnt signalling antagonizes stress granule assembly through a Dishevelled-dependent mechanism
title_fullStr	Wnt signalling antagonizes stress granule assembly through a Dishevelled-dependent mechanism
title_full_unstemmed	Wnt signalling antagonizes stress granule assembly through a Dishevelled-dependent mechanism
title_sort	wnt signalling antagonizes stress granule assembly through a dishevelled-dependent mechanism
description	Cells often respond to diverse environmental stresses by inducing stress granules (SGs) as an adaptive mechanism. SGs are generally assembled as a result of aggregation of mRNAs stalled in a translational pre-initiation complex, mediated by a set of RNA-binding proteins such as G3BP and TIA-1. SGs may serve as triage centres for storage, translation re-initiation or degradation of specific mRNAs. However, the mechanism involved in the modulation of their assembly/disassembly is unclear. Here we report that Wnt signalling negatively regulates SG assembly through Dishevelled (Dvl), a cytoplasmic Wnt effector. Overexpression of Dvl2, an isoform of Dvl, leads to impairment of SG assembly through a DEP domain dependent mechanism. Intriguingly, the Dvl2 mutant K446M, which corresponds to an analogous mutation in Drosophila Dishevelled DEP domain (dsh1) that results in defective PCP pathway, fails to antagonize SG assembly. Furthermore, we show that Dvl2 exerts the antagonistic effect on SG assembly through a mechanism involving Rac1-mediated inhibition of RhoA. Dvl2 interacts with G3BP, a downstream component of Ras signalling involved in SG assembly, and functional analysis suggests a model wherein the Dvl-Rac1-RhoA axis regulates G3BP's SG-nucleating activity. Collectively, these results define an antagonistic effect of Wnt signalling on SG assembly, and reveal a novel role for Wnt/Dvl pathway in the modulation of mRNA functions.
publisher	The Company of Biologists
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507204/
_version_	1611935666744066048

Wnt signalling antagonizes stress granule assembly through a Dishevelled-dependent mechanism

Similar Items