Leukocyte Adhesion Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.
PLoS One. 2012;7(6):e38517. doi: 10.1371/journal.pone.0038517. Epub 2012 Jun 11.
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.
Gαi 蛋白偶联趋化因子受体在免疫细胞定向迁移中的作用已被充分了解。在这项研究中，我们表明，Gαq/11 蛋白这一类独立的蛋白对于 T 细胞随机迁移和趋化因子依赖的定向迁移的基本能力是必需的。使用显性负 cDNA 构建体或针对 Gαq 的 siRNA 干扰 Gαq 或 Gα11 会导致 LFA-1 黏附的积累和迁移停滞。Gαq/11 对质膜水平的 LFA-1 表达及其内化有影响。此外，Gαq 与表达 LFA-1 和 EEA1 的细胞内囊泡部分共定位，但不与表达 Rap1 但不表达 Rab11 的囊泡共定位。然而，Gαq 的影响并不局限于表达它的囊泡，因为它的减少改变了参与循环的其他囊泡的细胞内运输。总之，与囊泡相关的 Gαq/11 对于 LFA-1 黏附的周转是必需的，而黏附的周转是迁移所必需的。这些 G 蛋白直接参与了循环的初始阶段，这对胞内体-胞吐途径的后期阶段有影响。
