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Title

β2-Chimaerin modulates CXCL12-dependent adhesion and chemotaxis in Jurkat T cells

AuthorsSiliceo, María; García-Bernal, David ; Carrasco, Silvia; Díaz-Flores, Ernesto; Leskow, Federico C.; Teixidó, Joaquín ; Kazanietz, Marcelo G.; Mérida, Isabel
KeywordsDiacylglycerol
C1 domain
Chemokines
Immune response
Rac GTPases
Issue Date1-Jan-2006
PublisherCompany of Biologists
CitationJournal of Cell Science, 119 (1) : 141-152 (2006)
AbstractThe small GTPase Rac contributes to regulation of cytoskeletal rearrangement during chemokine-induced lymphocyte adhesion and migration in a multi-step process that is very precisely coordinated. Chimaerins are Rac1-specific GTPase-activating proteins of unknown biological function, which have a canonical diacylglycerol C1-binding domain. Here we demonstrate endogenous expression of β2-chimaerin in T lymphocytes and study the functional role of this protein in phorbol ester and chemokine (CXCL12)-regulated T-cell responses. We used green fluorescent protein-tagged β2-chimaerin and phorbol ester stimulation to investigate changes in protein localization in living lymphocytes. Our results demonstrate that active Rac cooperates with C1-dependent phorbol ester binding to induce sustained GFP-β2-chimaerin localization to the membrane. Subcellular distribution of GFP β2-chimaerin in living cells showed no major changes following CXCL12 stimulation. Nonetheless Rac1-GTP levels were severely inhibited in GFP-β2-chimaerin-expressing cells, which displayed reduced CXCL12-induced integrin-dependent adhesion and spreading. This effect was dependent on chimaerin GTPase-activating protein function and required diacylglycerol generation. Whereas β2-chimaerin overexpression decreased static adhesion, it enhanced CXCL12-dependent migration via receptor-dependent diacylglycerol production. These studies demonstrate that β2-chimaerin provides a novel, diacylglycerol-dependent mechanism for Rac regulation in T cells and suggest a functional role for this protein in Rac-mediated cytoskeletal remodeling
Description12 páginas, 9 figuras -- PAGS nros. 141-152
Publisher version (URL)http://dx.doi.org/10.1242/​jcs.02722
URIhttp://hdl.handle.net/10261/72248
DOI10.1242/​jcs.02722
ISSN0021-9533
E-ISSN1477-9137
Appears in Collections:(CIB) Artículos
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