A5010723935- Cellular transport and secretion
- Calcium signaling and nucleotide metabolism
- Autophagy in Disease and Therapy
- Lipid Membrane Structure and Behavior
- Erythrocyte Function and Pathophysiology
- Biomedical Research and Pathophysiology
- Heat shock proteins research
- Pancreatic function and diabetes
- Endoplasmic Reticulum Stress and Disease
- Bacterial Genetics and Biotechnology
- Infectious Disease Case Reports and Treatments
- Mast cells and histamine
- Lysosomal Storage Disorders Research
- Trypanosoma species research and implications
- Glycosylation and Glycoproteins Research
- Urticaria and Related Conditions
- Infections and bacterial resistance
University of Bonn
2010-2024
Max Planck Institute for Biophysical Chemistry
2010
The transfer of endocytosed cargoes to lysosomes (LYSs) requires HOPS, a multiprotein complex that tethers late endosomes (LEs) LYSs before fusion. Many proteins interact with HOPS on LEs/LYSs. However, it is not clear whether these interactors localize LEs or how they participate in tethering. Here, we biochemically characterized purified from untreated experimentally manipulated cells put and interacting order establish their functional interdependence. Our results assign Rab2a Rab7 Arl8...
Significance Phagocytes are key to innate immunity, as they ingest, kill, and degrade foreign particles, such microbes. Particle uptake results in the formation of phagosomes that eventually fuse with lysosomes, main degradative compartments cells. Phagosome–lysosome fusion (PLF) is crucial for degradation phagosome contents antigen presentation. Most pathogenic microbes multiply within phagocytes cause severe diseases (e.g. tuberculosis), prevent PLF. Deciphering mechanisms govern PLF will...
Professional phagocytic cells such as macrophages are a central part of innate immune defence. They ingest microorganisms into membrane-bound compartments (phagosomes), which acidify and eventually fuse with lysosomes, exposing their contents to microbicidal environment. Gram-positive Rhodococcus equi can cause pneumonia in young foals immunocompromised humans. The possession virulence plasmid allows them subvert host defence mechanisms multiply macrophages. Here, we show that the...
Uptake of microorganisms by professional phagocytic cells leads to formation a new subcellular compartment, the phagosome, which matures sequential fusion with early and late endocytic compartments, resulting in oxidative nonoxidative killing enclosed microbe. Few tools are available study membrane between compartments general pathogen-containing phagosomes particular. We have developed applied fluorescence microscopy assay microbe-containing different-aged vitro. This revealed that...
Phagosomes mature into phagolysosomes by sequential fusion with early endosomes, late and lysosomes. Phagosome-with-lysosome (PLF) results in the delivery of lysosomal hydrolases phagosomes digestion cargo. The machinery that drives PLF has been little investigated. Using a cell-free system, we recently identified phosphoinositide lipids (PIPs) phosphatidylinositol 3-phosphate (PI(3)P) 4-phosphate (PI(4)P) as regulators PLF. We now report identification PIP requirements four distinct...
Proteome maintenance in contracting skeletal and cardiac muscles depends on the chaperone-regulating protein BAG3. Reduced BAG3 activity leads to muscle weakness heart failure animal models patients. its chaperone partners recognize mechanically damaged proteins initiate their disposal through chaperone-assisted selective autophagy (CASA). However, molecular details of force-dependent regulation have remained elusive so far. Here, we demonstrate that mechanical stress triggers...
Several ATP- and cytosol-dependent fusion processes between membranes of the endocytic exocytic pathways have been biochemically reconstituted. Here, we present a phagosome-lysosome reaction that is driven by micromolar concentrations Ca2+ in absence ATP cytosol. Investigating classical Ca2+-driven (CaFu) side-by-side vitro, using same membrane preparations, show CaFu faster than standard (StaFu), leads to larger products not blocked established inhibitors StaFu. A concentration ∼120 µM...