Signal transduction from endosomes/lysosomes to the cytoskeleton during phagocytosis

• Antragsteller: Professor Dr. Markus Maniak
• Fachliche Zuordnung: Zellbiologie
• Förderung: Förderung von 2006 bis 2011
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 31640869

Many cells take up particles from their environment. Within phagosomes, particles mature gradually fusing with organelles of different molecular compositions. Enzymes degrade the internalized macromolecules in order to provide fuel for the cellular metabolism. Scattered observations indicate that trafficking routes and maturation velocities of phagosomes are much more heterogeneous than previously anticipated. Griffiths¿ new concept of ¿phagosome individuality¿ predicts signalling from phagosomes into the cytoplasm, which could regulate many aspects of cell physiology. We have noted that mutants lacking a component of the machinery required to degrade internalized bacteria, or overexpressing another, compensate by increasing the rate of food uptake. Because these are two examples of signalling from the phagosome to the machinery needed for particle uptake, we have performed gene-expression profiling of these mutant cell lines, and identified common candidate genes that are misregulated and therefore may be involved in the signalling process. We propose to study the effect of these genes if misregulated artificially by overexpression or negative genetic interference. If such a mutant is altered in its phagocytic properties, we will find out where in the cell the gene product localizes and whether it influences the expression of other genes identified in the same screen. By these means we should be able to reconstruct at least part of the hitherto obscure signalling cascade from endosomes to the cytoskeletal machinery that mediates internalization at the plasma membrane.

• DFG-Verfahren: Sachbeihilfen