title: PKCepsilon induces astrocyte stellation by modulating multiple cytoskeletal proteins and interacting with Rho A signalling pathways: implications for neuroinflammation.
abstract: Despite the importance of stellation to maintain astrocyte functionality, the intracellular signals controlling morphology in these cells are poorly characterized. Our goal was to examine the implication of protein kinase C epsilon (PKCepsilon) in astrocyte stellation. We found that the morphological transformation of astrocytes induced by exposure to the pro-inflammatory agent lipopolysaccharide is enhanced by adenoviral expression of wild-type PKCepsilon, and that activation of PKCepsilon is sufficient to trigger a dramatic stellation. Such an effect is mediated by the rearrangement of microtubules and filaments of glial fibrillary acidic protein, disorganization of stress fibres, and formation of new actin filaments within growing cellular processes. Furthermore, PKCepsilon regulates actin-interacting elements such as non-muscle myosin and proteins of the ezrin/radixin/moesin family. We also observed that at least part of the actions of PKCepsilon depend on its catalytic activity. Finally, stellation by PKCepsilon could be blocked by the expression of a constitutively active form of Rho A implicated in the stability of the flat astrocytic morphology. In summary, PKCepsilon stands out as a key intracellular regulator of morphological plasticity in astrocytes, affecting a large range of cytoskeletal elements and inactivating Rho A-dependent pathways. These morphological effects of PKCepsilon may play essential roles during the course of neuroinflammation.
authors.affiliation: Medical School and Regional Center for Biomedical Research (CRIB), Castilla-La Mancha University, C/Almansa 14, Albacete 02006, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Burgos
authors.forename: Soledad
authors.initials: S
authors.lastname: Calvo
authors.forename: Francisca
authors.initials: F
authors.lastname: Molina
authors.forename: Cecilia F
authors.initials: CF
authors.lastname: Vaquero
authors.forename: Allen
authors.initials: A
authors.lastname: Samarel
authors.forename: Juan
authors.initials: J
authors.lastname: Llopis
authors.forename: Pedro
authors.initials: P
authors.lastname: Tranque
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D016296:Mutagenesis / Q000502:physiology; D051744:Protein Kinase C-epsilon / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D051744:Protein Kinase C-epsilon; D020742:rhoA GTP-Binding Protein