Modulation of the Phagosome Proteome by Interferon-γ

Jutras, Isabelle; Houde, Mathieu; Currier, Nathan; Boulais, Jonathan; Duclos, Sophie; Laboissiere, Sylvie; Bonneil, Éric; Kearney, Paul; Thibault, Pierre; Paramithiotis, Eustache; Hugo, Patrice; Desjardins, Michel

doi:10.1074/mcp.m700267-mcp200

Cited by 72 publications

(79 citation statements)

References 45 publications

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“…Overexpression of marker proteins such as Rab5, Rab7, or Rab9 enhanced this colocalization. Other groups have already identified certain GBPs on phagocytosed latex bead (42,43) and bacteria (44,45). In some cases, we observed recruitment of hGBP1 very early during formation of phagocytic cups.…”

Section: Discussionmentioning

confidence: 86%

Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1

Shydlovskyi

Zienert

İnce

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

120

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Dynamin-like proteins (DLPs) mediate various membrane fusion and fission processes within the cell, which often require the polymerization of DLPs. An IFN-inducible family of DLPs, the guanylate-binding proteins (GBPs), is involved in antimicrobial and antiviral responses within the cell. Human guanylate-binding protein 1 (hGBP1), the founding member of GBPs, is also engaged in the regulation of cell adhesion and migration. Here, we show how the GTPase cycle of farnesylated hGBP1 (hGBP1F) regulates its self-assembly and membrane interaction. Using vesicles of various sizes as a lipid bilayer model, we show GTP-dependent membrane binding of hGBP1F. In addition, we demonstrate nucleotide-dependent tethering ability of hGBP1F. Furthermore, we report nucleotide-dependent polymerization of hGBP1F, which competes with membrane binding of the protein. Our results show that hGBP1F acts as a nucleotide-controlled molecular switch by modulating the accessibility of its farnesyl moiety, which does not require any supportive proteins.

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Section: Discussionmentioning

confidence: 86%

Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1

Shydlovskyi

Zienert

İnce

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

120

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“…1A). As expected, the late endosomal/lysosomal markers LAMP1 and Flotillin-1 both increased during phagosome maturation (10), while the cell surface marker Na,K-ATPase ␣ subunit and the NADPH oxidase gp91phox subunit both decreased with time (35). The proteins present in phagosomal membrane microdomains were separated into a Triton X-100-soluble fraction and a Triton X-100-resistant membrane fraction for each time point.…”

Section: Resultsmentioning

confidence: 99%

“…Accordingly, different sets of proteins have been shown to associates with maturing phagosomes and assigned to early or late phagosomes (4,5,44). More detailed analyses using proteomics led to the identification of a large group of proteins on phagosomes from different species and model organisms (6,7,35,40,(45)(46)(47)(48), providing unique insights into the potential functions of this organelle. One of the novel concepts derived from these studies was that phagosomes display membrane microdomains where specific proteins assemble (7,10,14).…”

Section: Discussionmentioning

confidence: 99%

Proteomic Characterization of Phagosomal Membrane Microdomains During Phagolysosome Biogenesis and Evolution

Goyette

Boulais

Carruthers

et al. 2012

Molecular & Cellular Proteomics

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After their formation at the cell surface, phagosomes become fully functional through a complex maturation process involving sequential interactions with various intracellular organelles. In the last decade, series of data indicated that some of the phagosome functional properties occur in specialized membrane microdomains. The molecules associated with membrane microdomains, as well as the organization of these structures during phagolysosome biogenesis are largely unknown. In this study, we combined proteomics and bioinformatics analyses to characterize the dynamic association of proteins to maturing phagosomes. Our data indicate that groups of proteins shuffle from detergent-soluble to detergent-resistant membrane microdomains during maturation, supporting a model in which the modulation of the phagosome functional properties involves an important reorganization of the phagosome proteome by the coordinated spatial segregation of proteins.

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“…IFN-␥ activation results in the transcriptional regulation of hundreds of genes including nitric oxide synthase-2 and phagocyte oxidase that are associated with the production of reactive oxygen species (ROS) and provide enhanced killing abilities to macrophages (6). This cytokine also mediates phagosome maturation and antigen loading on MHC class I and class II molecules (7)(8)(9)(10)(11). Alternate activation of macrophages by interleukin 4 (IL-4) and IL-13 cytokines produced by T-helper 2 cells has also been proposed to account for allergic, cellular, and humoral responses to parasitic and extracellular pathogens (12).…”

mentioning

confidence: 99%

Quantitative Proteomics Reveals the Induction of Mitophagy in Tumor Necrosis Factor-α-activated (TNFα) Macrophages

Bell

English

Boulais

et al. 2013

Molecular & Cellular Proteomics

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Macrophages play an important role in innate and adaptive immunity as professional phagocytes capable of internalizing and degrading pathogens to derive antigens for presentation to T cells. They also produce pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-␣) that mediate local and systemic responses and direct the development of adaptive immunity. The present work describes the use of label-free quantitative proteomics to profile the dynamic changes of proteins from resting and TNF-␣-activated mouse macrophages. These analyses revealed that TNF-␣ activation of macrophages led to the down-regulation of mitochondrial proteins and the differential regulation of several proteins involved in vesicle trafficking and immune response. Importantly, we found that the down-regulation of mitochondria proteins occurred through mitophagy and was specific to TNF-␣, as other cytokines such as IL-1␤ and IFN-␥ had no effect on mitochondria degradation. Furthermore, using a novel antigen presentation system, we observed that the induction of mitophagy by TNF-␣ enabled the processing and presentation of mitochondrial antigens at the cell surface by MHC class I molecules. These findings highlight an unsuspected role of TNF-␣ in mitophagy and expanded our understanding of the mechanisms responsible for MHC presentation of self-antigens. Molecular & Cellular

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Modulation of the Phagosome Proteome by Interferon-γ

Cited by 72 publications

References 45 publications

Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1

Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1

Proteomic Characterization of Phagosomal Membrane Microdomains During Phagolysosome Biogenesis and Evolution

Quantitative Proteomics Reveals the Induction of Mitophagy in Tumor Necrosis Factor-α-activated (TNFα) Macrophages

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