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標題: RhoA inactivation is crucial to manganese-induced astrocyte stellation
作者: Chen, C.J.
Liao, S.L.
Huang, Y.S.
Chiang, A.N.
關鍵字: actin stress fibers;astrocytes;manganese;rho GTPases;stellation;rat cortical astrocytes;actin cytoskeleton;protein-kinase;lim-kinase;morphology;differentiation;neurons;gtpases
Project: Biochemical and Biophysical Research Communications
期刊/報告no:: Biochemical and Biophysical Research Communications, Volume 326, Issue 4, Page(s) 873-879.
Actin depolymerization through Rho GTPases or exogenous mechanical tension has been suggested as a key determinant for the formation of astrocyte stellation. Rho GTPases function as switching molecules to converge both extracellular and intracellular signals in regulation of cytoskeletal organization. Their involvement in manganese-induced astrocyte stellation was assessed. The disruption of cytoskeletal architecture by manganese indicated the decreased activity of RhoA. Pharmacological and biochemical approaches revealed the inactivation of RhoA by manganese. This inactivation was partly through the down-regulation of guanine nucleotide exchange factor phosphorylation. Furthermore, the dephosphorylation of myosin light chain and cofilin through the inactivated RhoA effectors synergistically destabilized actin stress fibers. We conclude that manganese regulates cytoskeletal organization in astrocytes by modulating the activity of p115RhoGEF and RhoA. (C) 2004 Elsevier Inc. All rights reserved.
ISSN: 0006-291X
DOI: 10.1016/j.bbrc.2004.11.121
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