RhoA inactivation is crucial to manganese-induced astrocyte stellation.
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.
Chen
Chun-Jung
CJ
Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan. cjchen@vghtc.gov.tw
Liao
Su-Lan
SL
Huang
Yong-San
YS
Chiang
An-Na
AN
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D002454:Cell Differentiation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D003599:Cytoskeleton / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure*; D004305:Dose-Response Relationship, Drug; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D020742:rhoA GTP-Binding Protein