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LC3 associated phagocytosis

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https://www.readbyqxmd.com/read/29029244/elmo1-regulates-the-induction-of-autophagy-and-bacterial-clearance-during-enteric-infection
#1
Arup Sarkar, Courtney Tindle, Rama F Pranadinata, Sharon Reed, Lars Eckmann, Thaddeus S Stappenbeck, Peter B Ernst, Soumita Das
Macrophages are specialized phagocytic cells involved in clearing invading pathogens. Earlier we reported the Engulfment and Cell Motility protein 1 (ELMO1) in macrophages mediates bacterial internalization and intestinal inflammation. Here we studied the role of ELMO1 in the fate of internalized target. ELMO1 is present in the intracellular vesicles and enhanced LC3B accumulation following engulfment of Salmonella or treatment with autophagy-inducing rapamycin. ATG5 and ULK1 are involved in classical autophagy while LC3-associated phagocytosis (LAP) is ULK1-independent...
October 5, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28973896/mycobacterium-tuberculosis-is-protected-from-nadph-oxidase-and-lc3-associated-phagocytosis-by-the-lcp-protein-cpsa
#2
Stefan Köster, Sandeep Upadhyay, Pallavi Chandra, Kadamba Papavinasasundaram, Guozhe Yang, Amir Hassan, Steven J Grigsby, Ekansh Mittal, Heidi S Park, Victoria Jones, Fong-Fu Hsu, Mary Jackson, Christopher M Sassetti, Jennifer A Philips
Mycobacterium tuberculosis' success as a pathogen comes from its ability to evade degradation by macrophages. Normally macrophages clear microorganisms that activate pathogen-recognition receptors (PRRs) through a lysosomal-trafficking pathway called "LC3-associated phagocytosis" (LAP). Although Mtuberculosis activates numerous PRRs, for reasons that are poorly understood LAP does not substantially contribute to Mtuberculosis control. LAP depends upon reactive oxygen species (ROS) generated by NADPH oxidase, but Mtuberculosis fails to generate a robust oxidative response...
September 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28933590/rubcn-rubicon-and-egfr-regulate-lysosomal-degradative-processes-in-the-retinal-pigment-epithelium-rpe-of-the-eye
#3
Luis Muniz-Feliciano, Teresa A Doggett, Zhenqing Zhou, Thomas A Ferguson
Macroautophagy/autophagy is an intracellular stress survival and recycling system whereas phagocytosis internalizes material from the extracellular milieu; yet, both pathways utilize lysosomes for cargo degradation. Whereas autophagy occurs in all cells, phagocytosis is performed by cell types such as macrophages and the retinal pigment epithelial (RPE) cells of the eye where it is supported by the noncanonical autophagy process termed LC3-associated phagocytosis (LAP). Autophagy and LAP are distinct pathways that use many of the same mediators and must compete for cellular resources, suggesting that cells may regulate both processes under homeostatic and stress conditions...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28928467/cross-talk-between-mir-471-5p-and-autophagy-component-proteins-regulates-lc3-associated-phagocytosis-lap-of-apoptotic-germ-cells
#4
Subbarayalu Panneerdoss, Suryavathi Viswanadhapalli, Nourhan Abdelfattah, Benjamin C Onyeagucha, Santosh Timilsina, Tabrez A Mohammad, Yidong Chen, Michael Drake, Kristiina Vuori, T Rajendra Kumar, Manjeet K Rao
Phagocytic clearance of apoptotic germ cells by Sertoli cells is vital for germ cell development and differentiation. Here, using a tissue-specific miRNA transgenic mouse model, we show that interaction between miR-471-5p and autophagy member proteins regulates clearance of apoptotic germ cells via LC3-associated phagocytosis (LAP). Transgenic mice expressing miR-471-5p in Sertoli cells show increased germ cell apoptosis and compromised male fertility. Those effects are due to defective engulfment and impaired LAP-mediated clearance of apoptotic germ cells as miR-471-5p transgenic mice show lower levels of Dock180, LC3, Atg12, Becn1, Rab5 and Rubicon in Sertoli cells...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28755428/safely-removing-cell-debris-with-lc3-associated-phagocytosis
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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