LC3-associated phagocytosis in microbial pathogenesis Schille, Stefan; Crauwels, Peter; Bohn, Rebecca ...
International journal of medical microbiology,
January 2018, 2018-Jan, 2018-01-00, 20180101, Letnik:
308, Številka:
1
Journal Article
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Phagocytosis is essential for uptake and elimination of pathogenic microorganisms. Autophagy is a highly conserved mechanism for incorporation of cellular constituents to replenish nutrients by ...degradation. Recently, parts of the autophagy machinery – above all microtubule-associated protein 1 light chain 3 (LC3) – were found to be specifically recruited to phagosomal membranes resulting in phagosome-lysosome fusion and efficient degradation of internalized cargo in a process termed LC3-associated phagocytosis (LAP). Many pathogenic bacterial, fungal and parasitic microorganisms reside within LAP-targeted single-membrane phagosomes or vacuoles after infection of host cells. In this minireview we describe the state of knowledge on the interaction of pathogens with LAP or LAP-like pathways and report on various pathogens that have evolved strategies to circumvent degradation in LAP compartments.
Hepatitis C virus (HCV) morphogenesis and release are closely linked to lipid metabolism. It has been described recently by our group that TIP47 plays an essential role for the targeting of the ...NS5A-complexed RNA genome from the replicon complex to the lipid droplet. Moreover, apolipoprotein (apo) E was found to be associated with the viral particle. In light of the fact, that TIP47 harbors an apoE like domain and has a high affinity to lipoproteins, the interaction of TIP47 with the viral particle and the potential relevance for the release of the viral particle were investigated. Coimmunoprecipitations and electron microscopy analysis using immunogold labeling revealed that TIP47 binds to the viral particle and stays associated with the released HCV particle. Silencing of the TIP47 binding partner Rab9 by lentiviral transduction abolishes the viral replication. However, destruction of TIP47-Rab9 interactions by deletion/mutation of the Rab9 binding does not abolish the genome replication domain but prevents the release of HCV particles. The binding of these TIP47 mutants to the viral particle is not affected by destruction of the Rab9 binding domain. Moreover, we found that these TIP47 mutants lacking the binding site for Rab9 misdirect the de novo synthesized viral particles to the autophagosomal/lysosomal compartment where the particles are degraded. From this we conclude that the Rab9-complexed TIP47 plays an essential role for the proper release of hepatitis C viral particles.
This article features with the enhancement of the static coefficient of friction by laser texturing the contact surfaces of tribological systems tested under dry friction conditions. The high-rate ...laser technology was applied for surface texturing at unprecedented processing rates, namely using powerful ultrashort pulses lasers in combination with ultrafast polygon-mirror based scan systems. The laser textured surfaces were analyzed by ion beam slope cutting and Raman measurements, showing a crystallographic disordering of the produced microscopic surface features. The laser induced self-organizing periodic surface structures as well as deterministic surface textures were tested regarding their tribological behavior. The highest static coefficient of friction was found of µ20 = 0.68 for a laser textured cross pattern that is 126% higher than for a fine grinded reference contact system. The line pattern was textured on a shaft-hub connection where the static coefficient of friction increased up to 75% that demonstrates the high potential of the technology for real-world applications.
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