ARF1 is directly involved in dynamin-independent endocytosis.
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.
Kumari
Sudha
S
National Centre for Biological Science (TIFR), Bellary Road, Bangalore 560 065, India.
Mayor
Satyajit
S
D020823:ADP-Ribosylation Factor 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D020126:Brefeldin A / Q000494:pharmacology; D016466:CHO Cells; D022461:Caveolins / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D034281:Dynamins / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D022461:Caveolins; D002966:Clathrin; D020690:GTPase-Activating Proteins; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D020126:Brefeldin A; D020823:ADP-Ribosylation Factor 1; D020764:cdc42 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; D034281:Dynamins