Glia maturation factor-gamma modulation of signaling pathways in macrophages

白细胞迁移需要整合素通过受调节的内-胞吐循环的动态再分布。胶质细胞成熟因子（GMFG）是Arp 2/3复合物的一种新的调节因子，已被证明是嗜中性粒细胞和T淋巴细胞有效定向迁移所必需的。在这里，我们研究了GMFG是否对人单核细胞迁移有类似的作用，以及GMFG作用的细胞机制。我们发现GMFG定位于早期内体（其中它与1-整联蛋白共定位）和晚期内体，以及内吞再循环隔室。单核细胞中GMFG的敲除延缓了1-整合素有效快速再循环回质膜，并显著增加了它们在静息和fMLF-或SDF-1-刺激的单核细胞中的降解。重要的是，GMFG的敲低导致细胞粘附减少，并损害单核细胞向化学引诱物fMLF和SDF-1的定向迁移。这些数据将GMFG鉴定为控制1-整联蛋白再循环及其降解以促进有效单核细胞迁移的分子开关。

Leukocyte migration requires the dynamic redistribution of integrins through a regulated endo-exocytosis cycle. Glia maturation factor-γ (GMFG), a novel regulator of the Arp2/3 complex, has been shown to be required for efficient directional migration of neutrophils and T-lymphocytes. Here, we investigated whether GMFG has similar effects on human monocyte migration, as well as the cellular mechanisms involved in GMFG action. We found that GMFG localizes to early endosomes (where it colocalizes with β1-integrins) and late endosomes, as well as the endocytic recycling compartment. Knockdown of GMFG in monocytes retarded the efficient rapid recycling of β1-integrins back to the plasma membrane and dramatically increased their degradation in both resting as well as fMLF- or SDF-1α-stimulated monocytes. Importantly, knockdown of GMFG results in reduced cell adhesion, and impaired directional migration of monocytes toward the chemoattractants fMLF and SDF-1α. These data identify GMFG as a molecular switch controlling β1-integrin recycling and its degradation to promote efficient monocyte migration.