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Role of Rho GTPase in astrocyte morphology and migratory response during in vitro wound healing

Item Type:Article
Title:Role of Rho GTPase in astrocyte morphology and migratory response during in vitro wound healing
Creators Name:Hoeltje, M. and Hoffmann, A. and Hofmann, F. and Mucke, C. and Grosse, G. and Van Rooijen, N. and Kettenmann, H. and Just, I. and Ahnert-Hilger, G.
Abstract:Small Rho GTPases are key regulators of the cytoskeleton in a great variety of cells. Rho function mediates morphological changes as well as locomotor activity. Using astrocyte cultures established from neonatal mice we investigated the role of Rho in process formation during astrocyte stellation. Using a scratch-wound model, we examined the impact of Rho on a variety of morphological and functional variables such as stellation and migratory activity during wound healing. C3 proteins are widely used to study cellular Rho functions. In addition, C3 derived from Clostridlum botulinum (C3 bot) is considered selectively to promote neuronal regeneration. Because the latter requires a balanced activity of neurones and glial cells, the effects of C3 protein on glial cells such as astrocytes have to be considered carefully. Low nanomolar concentrations of C3 proteins significantly promoted process outgrowth and increased process branching. Besides enzymatic inactivation of Rho by ADP-ribosylation, changes in protein levels of the various Rho GTPases may also contribute to the observed effects. Furthermore, incubation of scratch-wounded astrocyte cultures with C3 bot accelerated wound healing. By inhibiting the Rho downstream effector ROCK with the selective inhibitor Y27632 we were able to demonstrate that the accelerated wound closure resulted from both enhanced polarized process formation and increased migratory activity of astrocytes into the lesion site. These results suggest that Rho negatively regulates astrocytic process growth and migratory responses after injury and that its inactivation by C3 bot in nanomolar concentrations promotes astrocyte migration.
Keywords:Astrocyte, C3 Exoenzyme, Rho GTPase, Scratch Wound, Animals, Mice
Source:Journal of Neurochemistry
Publisher:Blackwell Publishing
Page Range:1237-1248
Date:7 September 2005
Official Publication:https://doi.org/10.1111/j.1471-4159.2005.03443.x
PubMed:View item in PubMed

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