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Negative regulation of RhoA translation and signaling by hnRNP-Q1 affects cellular morphogenesis

The small GTPase RhoA has critical functions in regulating actin dynamics affecting cellular morphogenesis through the RhoA/Rho kinase (ROCK) signaling cascade. RhoA signaling controls stress fiber and focal adhesion formation and cell motility in fibroblasts. RhoA signaling is involved in several a...

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Detalles Bibliográficos
Autores principales: Xing, Lei, Yao, Xiaodi, Williams, Kathryn R., Bassell, Gary J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327311/
https://www.ncbi.nlm.nih.gov/pubmed/22357624
http://dx.doi.org/10.1091/mbc.E11-10-0867
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author Xing, Lei
Yao, Xiaodi
Williams, Kathryn R.
Bassell, Gary J.
author_facet Xing, Lei
Yao, Xiaodi
Williams, Kathryn R.
Bassell, Gary J.
author_sort Xing, Lei
collection PubMed
description The small GTPase RhoA has critical functions in regulating actin dynamics affecting cellular morphogenesis through the RhoA/Rho kinase (ROCK) signaling cascade. RhoA signaling controls stress fiber and focal adhesion formation and cell motility in fibroblasts. RhoA signaling is involved in several aspects of neuronal development, including neuronal migration, growth cone collapse, dendrite branching, and spine growth. Altered RhoA signaling is implicated in cancer and neurodegenerative disease and is linked to inherited intellectual disabilities. Although much is known about factors regulating RhoA activity and/or degradation, little is known about molecular mechanisms regulating RhoA expression and the subsequent effects on RhoA signaling. We hypothesized that posttranscriptional control of RhoA expression may provide a mechanism to regulate RhoA signaling and downstream effects on cell morphology. Here we uncover a cellular function for the mRNA-binding protein heterogeneous nuclear ribonucleoprotein (hnRNP) Q1 in the control of dendritic development and focal adhesion formation that involves the negative regulation of RhoA synthesis and signaling. We show that hnRNP-Q1 represses RhoA translation and knockdown of hnRNP-Q1 induced phenotypes associated with elevated RhoA protein levels and RhoA/ROCK signaling. These morphological changes were rescued by ROCK inhibition and/or RhoA knockdown. These findings further suggest that negative modulation of RhoA mRNA translation can provide control over downstream signaling and cellular morphogenesis.
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spelling pubmed-33273112012-06-30 Negative regulation of RhoA translation and signaling by hnRNP-Q1 affects cellular morphogenesis Xing, Lei Yao, Xiaodi Williams, Kathryn R. Bassell, Gary J. Mol Biol Cell Articles The small GTPase RhoA has critical functions in regulating actin dynamics affecting cellular morphogenesis through the RhoA/Rho kinase (ROCK) signaling cascade. RhoA signaling controls stress fiber and focal adhesion formation and cell motility in fibroblasts. RhoA signaling is involved in several aspects of neuronal development, including neuronal migration, growth cone collapse, dendrite branching, and spine growth. Altered RhoA signaling is implicated in cancer and neurodegenerative disease and is linked to inherited intellectual disabilities. Although much is known about factors regulating RhoA activity and/or degradation, little is known about molecular mechanisms regulating RhoA expression and the subsequent effects on RhoA signaling. We hypothesized that posttranscriptional control of RhoA expression may provide a mechanism to regulate RhoA signaling and downstream effects on cell morphology. Here we uncover a cellular function for the mRNA-binding protein heterogeneous nuclear ribonucleoprotein (hnRNP) Q1 in the control of dendritic development and focal adhesion formation that involves the negative regulation of RhoA synthesis and signaling. We show that hnRNP-Q1 represses RhoA translation and knockdown of hnRNP-Q1 induced phenotypes associated with elevated RhoA protein levels and RhoA/ROCK signaling. These morphological changes were rescued by ROCK inhibition and/or RhoA knockdown. These findings further suggest that negative modulation of RhoA mRNA translation can provide control over downstream signaling and cellular morphogenesis. The American Society for Cell Biology 2012-04-15 /pmc/articles/PMC3327311/ /pubmed/22357624 http://dx.doi.org/10.1091/mbc.E11-10-0867 Text en © 2012 Xing et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Xing, Lei
Yao, Xiaodi
Williams, Kathryn R.
Bassell, Gary J.
Negative regulation of RhoA translation and signaling by hnRNP-Q1 affects cellular morphogenesis
title Negative regulation of RhoA translation and signaling by hnRNP-Q1 affects cellular morphogenesis
title_full Negative regulation of RhoA translation and signaling by hnRNP-Q1 affects cellular morphogenesis
title_fullStr Negative regulation of RhoA translation and signaling by hnRNP-Q1 affects cellular morphogenesis
title_full_unstemmed Negative regulation of RhoA translation and signaling by hnRNP-Q1 affects cellular morphogenesis
title_short Negative regulation of RhoA translation and signaling by hnRNP-Q1 affects cellular morphogenesis
title_sort negative regulation of rhoa translation and signaling by hnrnp-q1 affects cellular morphogenesis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327311/
https://www.ncbi.nlm.nih.gov/pubmed/22357624
http://dx.doi.org/10.1091/mbc.E11-10-0867
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