title: Regulation of astrocyte morphology by RhoA and lysophosphatidic acid.
abstract: Astrocytes in the CNS undergo morphological changes and start to proliferate after breakdown of the blood-brain barrier. In culture, proliferating astrocytes have a flat, polygonal shape. When treated with cAMP-raising agents, astrocytes adopt a stellate, process-bearing morphology resembling their in vivo appearance. Stellation is accompanied by loss of actin stress fibers and focal adhesions. Lysophosphatidic acid (LPA), a blood-borne mitogen that signals through its cognate G protein-coupled receptor, stimulates DNA synthesis in astrocytes and causes rapid reversal of cAMP-induced stellation. LPA reversal of stellation is initiated by f-actin reassembly and tyrosine phosphorylation of focal adhesion proteins such as paxillin. Botulinum C3 toxin, which inactivates the Rho GTPase, mimics cAMP-raising agents in inducing stellation, f-actin disassembly, paxillin dephosphorylation, and growth arrest. However, unlike cAMP-induced stellation, C3-induced stellation cannot be reversed by LPA. Conversely, astrocytes expressing activated RhoA fail to undergo cAMP-induced stellation. Thus, RhoA controls astrocyte morphology in that active RhoA directs LPA reversal of stellation, while inactivation of RhoA is sufficient to induce stellation.
authors.affiliation: Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Ramakers
authors.forename: W H
authors.initials: WH
authors.lastname: Moolenaar
mesh_terms: D036002:ADP Ribose Transferases / Q000494:pharmacology; D000199:Actins / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects; D001905:Botulinum Toxins; D002448:Cell Adhesion / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000819:agonists / Q000502:physiology; D003571:Cytochalasin B / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D004247:DNA / Q000096:biosynthesis; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008246:Lysophospholipids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D016548:Prosencephalon; D051381:Rats; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D008246:Lysophospholipids; D051419:Paxillin; D010750:Phosphoproteins; C496063:Pxn protein, rat; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D019000:Phosphotyrosine; D003571:Cytochalasin B; D004247:DNA; D000242:Cyclic AMP; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D019950:Mitogen-Activated Protein Kinase 1; D001905:Botulinum Toxins; D019204:GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein