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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

Item Type:	Article
Authors/Creators:	Haas, MA and Vickers, JC and Dickson, TC
Keywords:	CNS; development; regeneration; migration; phosphorylation
Journal or Publication Title:	Journal of Neuroscience Research
Publisher:	John Wiley & Sons, Inc.
ISSN:	0360-4012
DOI / ID Number:	https://doi.org/10.1002/jnr.21102
Additional Information:	The original publication is available at http://www.interscience.wiley.com/
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