Human GBP1 Is Involved in the Repair of Damaged Phagosomes/Endolysosomes

被引:8
作者
Buijze, Hellen [1 ]
Brinkmann, Volker [2 ]
Hurwitz, Robert [3 ]
Dorhoi, Anca [4 ,5 ]
Kaufmann, Stefan H. E. [1 ,6 ,7 ]
Pei, Gang [4 ]
机构
[1] Max Planck Inst Infect Biol, Dept Immunol, Charite Pl 1, D-10117 Berlin, Germany
[2] Max Planck Inst Infect Biol, Microscopy Core Facil, Charite Pl 1, D-10117 Berlin, Germany
[3] Max Planck Inst Infect Biol, Prot Purificat Facil, Charite Pl 1, D-10117 Berlin, Germany
[4] Friedrich Loeffler Inst, Fed Res Inst Anim Hlth, Inst Immunol, D-17493 Greifswald, Germany
[5] Univ Greifswald, Fac Math & Nat Sci, D-17489 Greifswald, Germany
[6] Max Planck Inst Multidisciplinary Sci, Emeritus Grp Syst Immunol, Fassberg 11, D-37077 Gottingen, Germany
[7] Texas A&M Univ, Hagler Inst Adv Study, College Stn, TX 77843 USA
关键词
guanylate-binding proteins; endolysosomal damage; Mycobacterium tuberculosis; Listeria monocytogenes; GUANYLATE-BINDING-PROTEINS; PATHOGEN-CONTAINING VACUOLES; LEUCINE METHYL-ESTER; HOST-DEFENSE; PHOSPHATIDYLINOSITOL; 4-KINASES; INFLAMMATORY CYTOKINES; NUCLEOTIDE-BINDING; AIM2; INFLAMMASOME; ACTIVATION; GALECTIN-3;
D O I
10.3390/ijms24119701
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mouse guanylate-binding proteins (mGBPs) are recruited to various invasive pathogens, thereby conferring cell-autonomous immunity against these pathogens. However, whether and how human GBPs (hGBPs) target M. tuberculosis (Mtb) and L. monocytogenes (Lm) remains unclear. Here, we describe hGBPs association with intracellular Mtb and Lm, which was dependent on the ability of bacteria to induce disruption of phagosomal membranes. hGBP1 formed puncta structures which were recruited to ruptured endolysosomes. Furthermore, both GTP-binding and isoprenylation of hGBP1 were required for its puncta formation. hGBP1 was required for the recovery of endolysosomal integrity. In vitro lipid-binding assays demonstrated direct binding of hGBP1 to PI4P. Upon endolysosomal damage, hGBP1 was targeted to PI4P and PI(3,4)P2-positive endolysosomes in cells. Finally, live-cell imaging demonstrated that hGBP1 was recruited to damaged endolysosomes, and consequently mediated endolysosomal repair. In summary, we uncover a novel interferon-inducible mechanism in which hGBP1 contributes to the repair of damaged phagosomes/endolysosomes.
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页数:19
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