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

• Type of Material: Article
• Authors: Lei Xing, Emory University; Xiaodi Yao, Emory University; Kathryn R. Williams, Emory University; Gary Bassell, Emory University
• Language: English
• Date: 2012-04-15
• Publisher: American Society for Cell Biology
• Publication Version: Final Published Version
• Copyright Statement: © 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).
• License: Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
• Final Published Version (URL): http://www.molbiolcell.org/content/23/8/1500
• Title of Journal or Parent Work: Molecular Biology of the Cell
• ISSN: 1059-1524
• Volume: 23
• Issue: 8
• Start Page: 1500
• End Page: 1509
• Grant/Funding Information: This research project was supported in part by Viral Vector Core and Microscopy Core of the Emory Neuroscience NINDS (NIH) Core Facilities grant P30NS055077.; This work was supported by aid from the Muscular Dystrophy Association (to G.J.B.) and National Institutes of Health (NIH) Training Grant T32GM008367-21 (for K.R.W.).
• Research Categories: Biology, Molecular; Biology, Cell; Biology, Neuroscience

Abstract

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.