The G?q/11 proteins contribute to T lymphocyte migration by promoting turnover of integrin LFA-1 through recycling.

ABSTRACT: The role of G?i proteins coupled to chemokine receptors in directed migration of immune cells is well understood. In this study we show that the separate class of G?q/11 proteins is required for the underlying ability of T cells to migrate both randomly and in a directed chemokine-dependent manner. Interfering with G?q or G?11 using dominant negative cDNA constructs or siRNA for G?q causes accumulation of LFA-1 adhesions and stalled migration. G?q/11 has an impact on LFA-1 expression at plasma membrane level and also on its internalization. Additionally G?q co-localizes with LFA-1- and EEA1-expressing intracellular vesicles and partially with Rap1- but not Rab11-expressing vesicles. However the influence of G?q 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 G?q/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.

SUBMITTER: Svensson L 

PROVIDER: S-EPMC3372505 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature