Cutting edge: FYCO1 recruitment to dectin-1 phagosomes is accelerated by light chain 3 protein and regulates phagosome maturation and reactive oxygen production.
L chain 3 (LC3)-associated phagocytosis is a process in which LC3, a protein canonically involved in engulfing intracellular materials (autophagy), is recruited to traditional phagosomes during internalization of extracellular payloads. LC3's association with phagosomes has been implicated in regulating microbial killing, Ag processing, and phagosome maturation; however, the mechanism by which LC3 influences these processes has not been clear. In this study, we report that FYVE and coiled-coil domain containing 1 (FYCO1), a protein previously implicated in autophagosome trafficking, is recruited directly by LC3 to Dectin-1 phagosomes. During LC3-associated phagocytosis, FYCO1 recruitment facilitates maturation of early p40phox(+) phagosomes into late LAMP1(+) phagosomes. When FYCO1 is lacking, phagosomes stay p40phox(+) longer and produce more reactive oxygen.
F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048;
Jun
J
Ma
Courtney
C
Becker
Christopher
C
Reyes
David M
DM
Underhill
D000818:Animals; D001343:Autophagy; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D003713:Dendritic Cells; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism*; D051907:Lysosomal Membrane Proteins / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis / Q000235:genetics; D010588:Phagosomes / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D000099181:Dectin-1; D052118:Lysosomal-Associated Membrane Protein 1
D020662:Guanine Nucleotide Exchange Factors; D037181:Lectins, C-Type; D051907:Lysosomal Membrane Proteins; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D000099181:Dectin-1; C574715:FGD5 protein, mouse; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C480860:Map1lc3b protein, mouse; C085072:neutrophil cytosol factor 40K