The G[alpha]q/11 Proteins Contribute to T Lymphocyte Migration by Promoting Turnover of Integrin LFA-1 through Recycling

The role of G[alpha]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[alpha]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[alpha]q or G[alpha]11 using dominant negative cDNA constructs or siRNA for G[alpha]q causes accumulation of LFA-1 adhesions and stalled migration. G[alpha]q/11 has an impact on LFA-1 expression at plasma membrane level and also on its internalization. Additionally G[alpha]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[alpha]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[alpha]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.