PDF, Englisch Download (5MB) | Nutzungsbedingungen

Abstract

Abstract: Every day millions of cells die in the human body, because of injury, infection, or to maintain homeostasis. The most common way for cells to die is through a process of controlled cell death, apoptosis, through which the body eliminates superfluous, or potentially damaged cells. However, ultimately this material needs to be removed, through phagocytosis, to avoid inflammation and secondary necrosis. Professional phagocytes deal with this by engulfing and digesting a large number of apoptotic cells. The throughput of this process is estimated to be several times the phagocytes own biomass in a 24 hour period. Here, I investigate the process by which engulfed apoptotic cell material is dealt with. To this end I have developed a correlative light and electron microscopy workflow that allows us to target a specific cell inside the brain of a zebrafish larvae. I have also made use of state of the art single plane illumination microscopy for tracking of the dynamic events involved in this process. By studying microglia in the optic tectum of zebrafish during a developmental stage characterized by high neuronal apoptosis I have discovered a role for the sugar‐phosphate transporter Slc37a2 in shrinking phagosomes as well as a propensity for phagosomes to undergo fusion resulting in apoptotic corpses being trafficked towards a single compartment inside the cell. The broader relevance of these findings is expanded on through the development of a cell culture model to study this compartment which allowed us to characterize it in further detail. This compartment has a unique ultrastructure and a molecular signature indicating it is involved in lipid metabolism and possibly phagosome resolution.