eCite Digital Repository

Rho kinase activates ezrin-radixin-moesin (ERM) proteins and mediates their function in cortical neuron growth, morphology and motility in vitro

Citation

Haas, MA and Vickers, JC and Dickson, TC, Rho kinase activates ezrin-radixin-moesin (ERM) proteins and mediates their function in cortical neuron growth, morphology and motility in vitro, Journal of Neuroscience Research, 85, (1) pp. 34-46. ISSN 0360-4012 (2007) [Refereed Article]

DOI: doi:10.1002/jnr.21102

Abstract

The ezrin-radixin-moesin (ERM) family of proteins contribute to cytoskeletal processes underlying many vital cellular functions. Their previously elucidated roles in non-neuronal cells are an indication of their potential importance in CNS neurons. The specific mechanisms of their activation are unknown, but are likely to depend on factors such as the cell type and biological context. For ERM proteins to become active they must be phosphorylated at a specific C-terminal threonine residue. In non-neuronal cells, several kinases, including the Rho GTPase family member Rho kinase, have been identified as capable of phosphorylating the C-terminal threonine. In these experiments we have investigated specifically the potential role of Rho kinase mediated ERM activation in cortical neurons, utilizing a new pharmacologic inhibitor of Rho kinase and quantitative analysis of aspects of neuronal functions potentially mediated by ERM proteins. Rho kinase inhibition significantly suppressed aspects of neuronal development including neurite initiation and outgrowth, as well as growth cone morphology, with a concomitant loss of phosphorylated ERM immunolabeling in areas associated with neuronal growth. The ability of the Rho kinase inhibitor to decrease the amount of pERM protein was shown by immunoblotting. Post-injury responses were negatively affected by Rho kinase inhibition, namely by a significant decrease in the number of regenerative neurites. We investigated a novel role for ERM proteins in neuron migration using a post-injury motility assay, where Rho kinase inhibition resulted in significant and drastic reduction in neuron motility and phosphorylated ERM immunolabeling. Thus, Rho kinase is an important activator of ERMs in mediating specific neuronal functions. © 2006 Wiley-Liss, Inc.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurology and Neuromuscular Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Haas, MA (Dr Matilda Haas)
Author:Vickers, JC (Professor James Vickers)
Author:Dickson, TC (Professor Tracey Dickson)
ID Code:46805
Year Published:2007
Web of Science® Times Cited:36
Deposited By:Menzies Institute for Medical Research
Deposited On:2007-08-01
Last Modified:2009-09-10
Downloads:0

Repository Staff Only: item control page