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LC3 associated phagocytosis

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https://www.readbyqxmd.com/read/28755428/safely-removing-cell-debris-with-lc3-associated-phagocytosis
#1
REVIEW
Gholamreza Fazeli, Ann Marie Wehman
Phagocytosis and autophagy are two distinct pathways that degrade external and internal unwanted particles. Both pathways lead to lysosomal degradation inside the cell, and over the last decade, the line between them has blurred; autophagy proteins were discovered on phagosomes engulfing foreign bacteria, leading to the proposal of LC3-associated phagocytosis (LAP). Many proteins involved in macroautophagy are used for phagosome degradation, although Atg8/LC3 family proteins only decorate the outer membrane of LC3-associated phagosomes, in contrast to both autophagosome membranes...
July 28, 2017: Biology of the Cell
https://www.readbyqxmd.com/read/28716903/autophagy-related-protein-vps34-controls-the-homeostasis-and-function-of-antigen-cross-presenting-cd8%C3%AE-dendritic-cells
#2
Vrajesh V Parekh, Sudheer K Pabbisetty, Lan Wu, Eric Sebzda, Jennifer Martinez, Jianhua Zhang, Luc Van Kaer
The class III PI3K Vacuolar protein sorting 34 (Vps34) plays a role in both canonical and noncanonical autophagy, key processes that control the presentation of antigens by dendritic cells (DCs) to naive T lymphocytes. We generated DC-specific Vps34-deficient mice to assess the contribution of Vps34 to DC functions. We found that DCs from these animals have a partially activated phenotype, spontaneously produce cytokines, and exhibit enhanced activity of the classic MHC class I and class II antigen-presentation pathways...
August 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28415949/%C3%AE-catenin-promotes-intracellular-bacterial-killing-via-suppression-of-pseudomonas-aeruginosa-triggered-macrophage-autophagy
#3
Qiang Fu, Kang Chen, Qian Zhu, Weijia Wang, Fuda Huang, Lishao Miao, Xinger Wu
Objective To investigate β-catenin-mediated bacterial elimination during Pseudomonas aeruginosa infection of macrophage-like RAW264.7 cells. Methods Cell viability and catenin beta 1 ( CTNNB1) expression in RAW264.7 cells following P. aeruginosa infection versus uninfected cells, were detected by cell counting kit-8 assay and β-catenin Western blots. RAW264.7 cells with CTNNB1 overexpression were established with β-catenin lentivirus using flow cytometry and clonogenic limiting dilution assays. Bacterial killing was measured by plate counts; phagocytosis and nitric oxide (NO) were measured by flow cytometry; and reactive oxygen species (ROS) were measured using Griess reaction...
April 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28413119/the-two-dictyostelium-discoideum-autophagy-8-proteins-have-distinct-autophagic-functions
#4
Susanne Meßling, Jan Matthias, Qiuhong Xiong, Sarah Fischer, Ludwig Eichinger
Autophagy is a highly conserved cellular degradation pathway which is crucial for various cellular processes. The autophagic process is subdivided in the initiation, autophagosome maturation and lysosomal degradation phases and involves more than forty core and accessory autophagy-related (ATG) proteins. Autophagy 8 (ATG8, in mammals LC3) is a well-established marker of autophagy and is linked to the autophagic membrane from initiation until fusion with the lysosome. We generated single and double knock-out mutants of the two Dictyostelium paralogues, ATG8a and ATG8b, as well as strains that expressed RFP-ATG8a and/or GFP-ATG8b, RFP-ATG8b, RFP-GFP-ATG8a or RFP-GFP-ATG8b in different knock-out mutants...
April 4, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28358370/the-role-of-autophagy-in-asparaginase-induced-immune-suppression-of-macrophages
#5
Ping Song, Ziyu Wang, Xuyao Zhang, Jiajun Fan, Yubin Li, Qicheng Chen, Shaofei Wang, Peipei Liu, Jingyun Luan, Li Ye, Dianwen Ju
Erwinia asparaginase, a bacteria-derived enzyme drug, has been used in the treatment of various cancers, especially acute lymphoblastic leukemia (ALL). One of the most significant side effects associated with asparaginase administration is immune suppression, which limits its application in clinic. Macrophages are phagocytic immune cells and have a central role in inflammation and host defense. We reported here that asparaginase disturbed the function of macrophages including phagocytosis, proliferation, ROS and nitric oxide secretion, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) secretion, and major histocompatibility complex II (MHC-II) molecule expression, thus induced immune suppression in interferon-γ and lipopolysaccharide-stimulated macrophages...
March 30, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28317932/bacterial-secretion-system-skews-the-fate-of-legionella-containing-vacuoles-towards-lc3-associated-phagocytosis
#6
Andree Hubber, Tomoko Kubori, Cevayir Coban, Takeshi Matsuzawa, Michinaga Ogawa, Tsuyoshi Kawabata, Tamotsu Yoshimori, Hiroki Nagai
The evolutionarily conserved processes of endosome-lysosome maturation and macroautophagy are established mechanisms that limit survival of intracellular bacteria. Similarly, another emerging mechanism is LC3-associated phagocytosis (LAP). Here we report that an intracellular vacuolar pathogen, Legionella dumoffii, is specifically targeted by LAP over classical endocytic maturation and macroautophagy pathways. Upon infection, the majority of L. dumoffii resides in ER-like vacuoles and replicate within this niche, which involves inhibition of classical endosomal maturation...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28253971/the-use-of-dq-bsa-to-monitor-the-turnover-of-autophagy-associated-cargo
#7
L S Frost, A Dhingra, J Reyes-Reveles, K Boesze-Battaglia
There is increasing evidence documenting the critical role played by autophagic and autophagy-associated processes in maintaining cell homeostasis and overall systemic health. Autophagy is considered a degradative as well as a recycling pathway that relies on encapsulated intracellular components trafficking to and fusing with degradative compartments, including lysosomes. In this chapter, we describe the use of DQ™-BSA to study autophagosome-lysosome fusion as well as a means by which to analyze hybrid autophagic pathways...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28166684/pathogenic-mechanisms-of-ige-mediated-inflammation-in-self-destructive-autoimmune-responses
#8
Rachel Ettinger, Jodi L Karnell, Jill Henault, Santosh K Panda, Jeffrey M Riggs, Roland Kolbeck, Miguel A Sanjuan
Autoantibodies of the IgG subclass are pathogenic in a number of autoimmune disorders such as systemic lupus erythomatosus. The presence of circulating IgE autoantibodies in autoimmune patients has also been known for almost 40 years. Despite their role in allergies, IgE autoantibodies are not associated with a higher rate of atopy in these patients. However, recently they have been recognized as active drivers of autoimmunity through mechanisms involving the secretion of Type I interferons by plasmacytoid dendritic cells (pDC), the recruitment of basophils to lymph nodes, and the activation of adaptive immune responses through B and T cells...
February 2017: Autoimmunity
https://www.readbyqxmd.com/read/27978429/dapk1-keeps-the-peace-in-antifungal-inflammation
#9
Tonia Akoumianaki, Georgios Chamilos
Unabated inflammation and impaired antifungal immunity underlie genetic defects in NOX-2-dependent activation of LC3-associated phagocytosis (LAP). In this issue of Cell Host & Microbe, Oikonomou et al. (2016) identify a molecular link between IFN-γ/DAPK1 signaling, the proteosomal degradation pathway, and LAP that is critical for dampening Aspergillus-triggered immunopathology.
December 14, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27889463/noncanonical-fungal-autophagy-inhibits-inflammation-in-response-to-ifn-%C3%AE-via-dapk1
#10
Vasilis Oikonomou, Silvia Moretti, Giorgia Renga, Claudia Galosi, Monica Borghi, Marilena Pariano, Matteo Puccetti, Carlo A Palmerini, Lucia Amico, Alessandra Carotti, Lucia Prezioso, Angelica Spolzino, Andrea Finocchi, Paolo Rossi, Andrea Velardi, Franco Aversa, Valerio Napolioni, Luigina Romani
Defects in a form of noncanonical autophagy, known as LC3-associated phagocytosis (LAP), lead to increased inflammatory pathology during fungal infection. Although LAP contributes to fungal degradation, the molecular mechanisms underlying LAP-mediated modulation of inflammation are unknown. We describe a mechanism by which inflammation is regulated during LAP through the death-associated protein kinase 1 (DAPK1). The ATF6/C/EBP-β/DAPK1 axis activated by IFN-γ not only mediates LAP to Aspergillus fumigatus but also concomitantly inhibits Nod-like receptor protein 3 (NLRP3) activation and restrains pathogenic inflammation...
December 14, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27880899/lc3c-contributes-to-vpu-mediated-antagonism-of-bst2-tetherin-restriction-on-hiv-1-release-through-a-non-canonical-autophagy-pathway
#11
Ursula Madjo, Olivier Leymarie, Stéphane Frémont, Aurelia Kuster, Mélanie Nehlich, Sarah Gallois-Montbrun, Katy Janvier, Clarisse Berlioz-Torrent
BST2 (bone marrow stromal antigen 2)/tetherin is a restriction factor of enveloped viruses, which blocks the release of viral particles. HIV-1 encodes proteins that antagonize this innate barrier, including the accessory protein Vpu. Here, we investigate whether the autophagy pathway and/or ATG proteins are hijacked by HIV-1 Vpu to circumvent BST2 restriction of viral release. We report that BST2 and Vpu are present in LC3-positive compartments. We found that Vpu selectively interacts with the ATG8 ortholog LC3C through the Vpu L63VEM66 sequence...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27815878/analysis-of-lc3-associated-phagocytosis-and-antigen-presentation
#12
Laure-Anne Ligeon, Susana Romao, Christian Münz
The noncanonical macroautophagy pathway, LC3-associated phagocytosis (LAP) has recently emerged as an important catabolic process involved during exogenous antigen processing. It has been described that in human macrophages and dendritic cells the direct recruitment of LC3 to the phagosomal membrane is associated with its maturation impairment, allowing the stabilization of the cargo to prolong antigen presentation on major histocompatibility complex (MHC) class II molecules.In this chapter, we describe methods to monitor, manipulate, and understand the role of LAP during MHC class II presentation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27562069/c-elegans-midbodies-are-released-phagocytosed-and-undergo-lc3-dependent-degradation-independent-of-macroautophagy
#13
Gholamreza Fazeli, Michaela Trinkwalder, Linda Irmisch, Ann Marie Wehman
In animals, the midbody coordinates the end of cytokinesis when daughter cells separate through abscission. The midbody was thought to be sequestered by macroautophagy, but recent evidence suggests that midbodies are primarily released and phagocytosed. It was unknown, however, whether autophagy proteins play a role in midbody phagosome degradation. Using a protein degradation assay, we show that midbodies are released in Caenorhabditis elegans Released midbodies are known to be internalized by actin-driven phagocytosis, which we show requires the RAB-5 GTPase to localize the class III phosphoinositide 3-kinase (PI3K) complex at the cortex...
October 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27310610/autophagy-proteins-are-not-universally-required-for-phagosome-maturation
#14
Marija Cemma, Sergio Grinstein, John H Brumell
Phagocytosis plays a central role in immunity and tissue homeostasis. After internalization of cargo into single-membrane phagosomes, these compartments undergo a maturation sequences that terminates in lysosome fusion and cargo degradation. Components of the autophagy pathway have recently been linked to phagosome maturation in a process called LC3-associated phagocytosis (LAP). In this process, autophagy machinery is thought to conjugate LC3 directly onto the phagosomal membrane to promote lysosome fusion...
September 2016: Autophagy
https://www.readbyqxmd.com/read/27297234/lap-the-protector-against-autoimmunity
#15
Urmi Bandyopadhyay, Michael Overholtzer
The autophagy-related process LC3-Associated Phagocytosis, or LAP, is known to control the degradation of engulfed cells and microorganisms. Now Martinez et al. discover that LAP controls immune responses to dying cells and its inhibition leads to development of Systemic Lupus Erythematosus-like disease.
August 2016: Cell Research
https://www.readbyqxmd.com/read/27280768/leishmania-major-promastigotes-evade-lc3-associated-phagocytosis-through-the-action-of-gp63
#16
Christine Matte, Pierre-André Casgrain, Olivier Séguin, Neda Moradin, Wan Jin Hong, Albert Descoteaux
The protozoan Leishmania parasitizes macrophages and evades the microbicidal consequences of phagocytosis through the inhibition of phagolysosome biogenesis. In this study, we investigated the impact of this parasite on LC3-associated phagocytosis, a non-canonical autophagic process that enhances phagosome maturation and functions. We show that whereas internalization of L. major promastigotes by macrophages promoted LC3 lipidation, recruitment of LC3 to phagosomes was inhibited through the action of the parasite surface metalloprotease GP63...
June 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27185909/lap-like-process-as-an-immune-mechanism-downstream-of-ifn-%C3%AE-in-control-of-the-human-malaria-plasmodium-vivax-liver-stage
#17
COMMENT
Rachasak Boonhok, Nattawan Rachaphaew, Apisak Duangmanee, Pornpimol Chobson, Sittiporn Pattaradilokrat, Pongsak Utaisincharoen, Jetsumon Sattabongkot, Marisa Ponpuak
IFN-γ is a major regulator of immune functions and has been shown to induce liver-stage Plasmodium elimination both in vitro and in vivo. The molecular mechanism responsible for the restriction of liver-stage Plasmodium downstream of IFN-γ remains uncertain, however. Autophagy, a newly described immune defense mechanism, was recently identified as a downstream pathway activated in response to IFN-γ in the control of intracellular infections. We thus hypothesized that the killing of liver-stage malarial parasites by IFN-γ involves autophagy induction...
June 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27185357/lc3-associated-phagocytosis-a-crucial-mechanism-for-antifungal-host-defence-against-aspergillus-fumigatus
#18
REVIEW
Evelien G G Sprenkeler, Mark S Gresnigt, Frank L van de Veerdonk
LC3-associated phagocytosis (LAP) is a non-canonical autophagy pathway involved in the maturation of single-membrane phagosomes and subsequent killing of ingested pathogens by phagocytes. This pathway is initiated following recognition of pathogens by pattern recognition receptors and leads to the recruitment of LC3 into the phagosomal membrane. This form of phagocytosis is utilized for the antifungal host defence and is required for an efficient fungal killing. Here, we provide an overview of the LAP pathway and review the role of LAP in anti-Aspergillus host defence, as well as mechanisms induced by Aspergillus that modulate LAP to promote its survival in the host...
September 2016: Cellular Microbiology
https://www.readbyqxmd.com/read/27096368/noncanonical-autophagy-inhibits-the-autoinflammatory-lupus-like-response-to-dying-cells
#19
Jennifer Martinez, Larissa D Cunha, Sunmin Park, Mao Yang, Qun Lu, Robert Orchard, Quan-Zhen Li, Mei Yan, Laura Janke, Cliff Guy, Andreas Linkermann, Herbert W Virgin, Douglas R Green
Defects in clearance of dying cells have been proposed to underlie the pathogenesis of systemic lupus erythematosus (SLE). Mice lacking molecules associated with dying cell clearance develop SLE-like disease, and phagocytes from patients with SLE often display defective clearance and increased inflammatory cytokine production when exposed to dying cells in vitro. Previously, we and others described a form of noncanonical autophagy known as LC3-associated phagocytosis (LAP), in which phagosomes containing engulfed particles, including dying cells, recruit elements of the autophagy pathway to facilitate maturation of phagosomes and digestion of their contents...
May 5, 2016: Nature
https://www.readbyqxmd.com/read/27043636/the-role-of-autophagy-related-proteins-in-candida-albicans-infections
#20
REVIEW
Jenny M Tam, Michael K Mansour, Mridu Acharya, Anna Sokolovska, Allison K Timmons, Adam Lacy-Hulbert, Jatin M Vyas
Autophagy plays an important role in maintaining cell homeostasis by providing nutrients during periods of starvation and removing damaged organelles from the cytoplasm. A marker in the autophagic process is the reversible conjugation of LC3, a membrane scaffolding protein, to double membrane autophagosomes. Recently, a role for LC3 in the elimination of pathogenic bacteria and fungi, including Candida albicans (C. albicans), was demonstrated, but these organisms reside in single membrane phagosomes. This process is distinct from autophagy and is termed LC3-associated phagocytosis (LAP)...
2016: Pathogens
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