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|標題:||L-Glutamate activates RhoA GTPase leading to suppression of astrocyte stellation||作者:||Chen, C.J.
|關鍵字:||astrocytes;glutamate transporter;L-glutamate;manganese;stellation;rat cortical astrocytes;amino-acid transporter;lim-kinase;cytoskeletal dynamics;cultured astrocytes;actin cytoskeleton;nervous-system;high-affinity;cell biology;manganese||Project:||European Journal of Neuroscience||期刊/報告no：:||European Journal of Neuroscience, Volume 23, Issue 8, Page(s) 1977-1987.||摘要:||
The actin cytoskeleton is known to support cellular morphological changes. Rho family small GTPases function as switching molecules to promote the convergence of both extracellular and intracellular signals in regulating cytoskeletal organization. Evidence indicates that L-glutamate suppresses morphological changes of astrocytes over a broad spectrum. To test the possibility that L-glutamate affects cytoskeletal reorganization, we investigated its effect on morphological changes induced by manganese exposure. L-Glutamate concentration-dependently prevented and reversed manganese-induced astrocyte stellation and cytoskeletal disruption. The suppressive effect of L-glutamate on manganese-induced stellation was mediated by the activation of the glutamate transporter rather than ionotropic or metabotropic glutamate receptors. Pharmacological and biochemical approaches revealed the involvement of Ras homolog gene family, member A ( RhoA) activation in L-glutamate-mediated suppression of manganese-induced stellation. The activation of RhoA by L-glutamate was partly through the up-regulation of guanine nucleotide exchange factor phosphorylation and was abrogated by competitive nonsubstrate inhibitors. Furthermore, the hyperphosphorylation of myosin light chain and cofilin through the activation of RhoA following L-glutamate treatment synergistically stabilized actin stress fibres. These results suggest that manganese- induced stellation is suppressed by a mechanism involving glutamate transporters. Our in vitro findings also strongly indicate that astrocyte morphological plasticity is under the control of RhoA and that manganese and L-glutamate regulate astrocyte morphology by modulating this switching molecule under culture conditions.
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