title: RhoG regulates gene expression and the actin cytoskeleton in lymphocytes.
abstract: RhoG, a member of the Rho family of GTPases, has been implicated as a regulator of the actin cytoskeleton. In this study, we show a novel function for the small GTPase RhoG on the regulation of the interferon-gamma promoter and nuclear factor of activated T cells (NFAT) gene transcription in lymphocytes. Optimal function of RhoG for the expression of these genes requires a calcium signal, normally provided by the antigen receptor. In addition, RhoG potentiation of NFAT requires the indirect activity of Rac and Cdc42; however, pathways distinct from those activated by Rac and Cdc42 mediate RhoG activation of NFAT-dependent transcription. Using effector domain mutants of RhoG we found that its ability to potentiate NFAT-dependent transcription correlates with its capacity to increase actin polymerization, supporting the suggestion that NFAT-dependent transcription is an actin-dependent process. RhoG also promotes T-cell spreading on fibronectin, a property that is independent of its ability to enhance NFAT-dependent transcription. Hence, these results implicate RhoG in leukocyte trafficking and the control of gene expression induced in response to antigen encounter.
authors.affiliation: Laboratory for Lymphocyte Signalling and Development, Molecular Immunology Programme, The Babraham Institute, Cambridge, UK. elena.vigorito@bbsrc.ac.uk
authors.forename: Elena
authors.initials: E
authors.lastname: Vigorito
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Billadeu
authors.forename: Doris
authors.initials: D
authors.lastname: Savoy
authors.forename: Simon
authors.initials: S
authors.lastname: McAdam
authors.forename: Gina
authors.initials: G
authors.lastname: Doody
authors.forename: Phillipe
authors.initials: P
authors.lastname: Fort
authors.forename: Martin
authors.initials: M
authors.lastname: Turner
mesh_terms: D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D001402:B-Lymphocytes / Q000502:physiology / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D019169:Jurkat Cells; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D009154:Mutation; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology / Q000648:ultrastructure; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins
chemical_list: D000199:Actins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005353:Fibronectins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D014157:Transcription Factors; C496618:VAV1 protein, human; C075397:RHOG protein, human; D007371:Interferon-gamma; D020558:GTP Phosphohydrolases; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D002118:Calcium