LGI3 interacts with flotillin-1 to mediate APP trafficking and exosome formation.
We recently showed that leucine-rich glioma inactivated 3 (LGI3) mediates the internalization of beta-amyloid protein and transferrin, a well-known marker for clathrin-dependent endocytosis, in neural cells. These findings strongly suggest that LGI3 is involved in the endocytosis system in the brain; however, the precise function of LGI3 remains unclear. Here, we show that LGI3 interacts with flotillin-1 (Flo1), and RNA interference analysis shows that LGI3 stabilized Flo1, and Flo1 also stabilized LGI3 vice versa. Moreover, the downregulation of the LGI3/Flo1 complex altered beta-amyloid precursor protein trafficking directly to late endosomes and disrupted exosome formation, suggesting that LGI3 is involved not only in endocytosis but also in another intracellular transport system through binding with its co-factor such as Flo1.
Okabayashi
Sachi
S
Laboratory of Disease Control, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba-shi, Ibaraki 305-0843, Japan. kimura@nibio.go.jp
Kimura
Nobuyuki
N
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D055354:Exosomes / Q000378:metabolism*; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D055550:Protein Stability; D034622:RNA Interference
D016564:Amyloid beta-Protein Precursor; C511168:LGI3 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C106354:flotillins