Kumari Sudha, Mayor Satyajit
National Centre for Biological Science (TIFR), Bellary Road, Bangalore 560 065, India.
Nat Cell Biol. 2008 Jan;10(1):30-41. doi: 10.1038/ncb1666. Epub 2007 Dec 16.
Endocytosis of glycosylphosphatidyl inositol (GPI)-anchored proteins (GPI-APs) and the fluid phase takes place primarily through a dynamin- and clathrin-independent, Cdc42-regulated pinocytic mechanism. This mechanism is mediated by primary carriers called clathrin-independent carriers (CLICs), which fuse to form tubular early endocytic compartments called GPI-AP enriched endosomal compartments (GEECs). Here, we show that reduction in activity or levels of ARF1 specifically inhibits GPI-AP and fluid-phase endocytosis without affecting other clathrin-dependent or independent endocytic pathways. ARF1 is activated at distinct sites on the plasma membrane, and by the recruitment of RhoGAP domain-containing protein, ARHGAP10, to the plasma membrane, modulates cell-surface Cdc42 dynamics. This results in the coupling of ARF1 and Cdc42 activity to regulate endocytosis at the plasma membrane. These findings provide a molecular basis for a crosstalk of endocytosis with secretion by the sharing of a key regulator of secretory traffic, ARF1.
糖基磷脂酰肌醇(GPI)锚定蛋白(GPI-APs)和液相的内吞作用主要通过一种不依赖发动蛋白和网格蛋白、由Cdc42调节的胞饮机制进行。这种机制由称为非网格蛋白依赖载体(CLICs)的初级载体介导,它们融合形成称为富含GPI-AP的内体区室(GEECs)的管状早期内吞区室。在这里,我们表明ARF1活性或水平的降低特异性抑制GPI-AP和液相内吞作用,而不影响其他网格蛋白依赖或非依赖的内吞途径。ARF1在质膜上的不同位点被激活,并通过含RhoGAP结构域的蛋白ARHGAP10募集到质膜上,调节细胞表面Cdc42的动态变化。这导致ARF1和Cdc42活性的耦合,以调节质膜上的内吞作用。这些发现为通过共享分泌运输的关键调节因子ARF1实现内吞作用与分泌的相互作用提供了分子基础。