Niedergang Florence, Colucci-Guyon Emma, Dubois Thierry, Raposo Graca, Chavrier Philippe
Membrane and Cytoskeleton Dynamics Laboratory, UMR144 CNRS, Institut Curie, 26 rue d'Ulm, F-75248 Paris cedex 05, France.
J Cell Biol. 2003 Jun 23;161(6):1143-50. doi: 10.1083/jcb.200210069. Epub 2003 Jun 16.
Engulfment of particles by phagocytes is induced by their interaction with specific receptors on the cell surface, which leads to actin polymerization and the extension of membrane protrusions to form a closed phagosome. Membrane delivery from internal pools is considered to play an important role in pseudopod extension during phagocytosis. Here, we report that endogenous ADP ribosylation factor 6 (ARF6), a small GTP-binding protein, undergoes a sharp and transient activation in macrophages when phagocytosis was initiated via receptors for the Fc portion of immunoglobulins (FcRs). A dominant-negative mutant of ARF6 (T27N mutation) dramatically affected FcR-mediated phagocytosis. Expression of ARF6-T27N lead to a reduction in the focal delivery of vesicle-associated membrane protein 3+ endosomal recycling membranes at phagocytosis sites, whereas actin polymerization was unimpaired. This resulted in an early blockade in pseudopod extension and accumulation of intracellular vesicles, as observed by electron microscopy. We conclude that ARF6 is a major regulator of membrane recycling during phagocytosis.
吞噬细胞对颗粒的吞噬作用是由它们与细胞表面特定受体的相互作用所诱导的，这会导致肌动蛋白聚合以及膜突起的延伸，从而形成一个封闭的吞噬体。来自内部池的膜转运被认为在吞噬作用期间的伪足延伸中起重要作用。在此，我们报告，内源性ADP核糖基化因子6（ARF6），一种小GTP结合蛋白，在巨噬细胞通过免疫球蛋白Fc部分的受体（FcRs）启动吞噬作用时会经历急剧且短暂的激活。ARF6的显性负性突变体（T27N突变）显著影响FcR介导的吞噬作用。ARF6-T27N的表达导致吞噬作用位点处囊泡相关膜蛋白3 + 内体循环膜的局部转运减少，而肌动蛋白聚合未受损害。如通过电子显微镜观察到的，这导致伪足延伸的早期阻断和细胞内囊泡的积累。我们得出结论，ARF6是吞噬作用期间膜循环的主要调节因子。
