The Gαq/11 proteins contribute to T lymphocyte migration by promoting turnover of integrin LFA-1 through recycling.
The role of Gαi proteins coupled to chemokine receptors in directed migration of immune cells is well understood. In this study we show that the separate class of Gαq/11 proteins is required for the underlying ability of T cells to migrate both randomly and in a directed chemokine-dependent manner. Interfering with Gαq or Gα11 using dominant negative cDNA constructs or siRNA for Gαq causes accumulation of LFA-1 adhesions and stalled migration. Gαq/11 has an impact on LFA-1 expression at plasma membrane level and also on its internalization. Additionally Gαq co-localizes with LFA-1- and EEA1-expressing intracellular vesicles and partially with Rap1- but not Rab11-expressing vesicles. However the influence of Gαq is not confined to the vesicles that express it, as its reduction alters intracellular trafficking of other vesicles involved in recycling. In summary vesicle-associated Gαq/11 is required for the turnover of LFA-1 adhesion that is necessary for migration. These G proteins participate directly in the initial phase of recycling and this has an impact on later stages of the endo-exocytic pathway.
Leukocyte Adhesion Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.
Lena
L
Svensson
Paula
P
Stanley
Frances
F
Willenbrock
Nancy
N
Hogg
D000911:Antibodies, Monoclonal; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology*; D018076:DNA, Complementary / Q000235:genetics; D005453:Fluorescence; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D047569:Laser Scanning Cytometry; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism*; D018715:Microscopy, Video; D034741:RNA, Small Interfering / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D057900:Transcytosis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D016169:Lymphocyte Function-Associated Antigen-1; D034741:RNA, Small Interfering; D043802:GTP-Binding Protein alpha Subunits, Gq-G11