The endolysosomal system comprises a dynamic constellation of vesicles working together to sense and interpret environmental cues and facilitate homeostasis. Integrating extracellular information... Show moreThe endolysosomal system comprises a dynamic constellation of vesicles working together to sense and interpret environmental cues and facilitate homeostasis. Integrating extracellular information with the internal affairs of the cell requires endosomes and lysosomes to be proficient in decision-making: fusion or fission; recycling or degradation; fast transport or contacts with other organelles. To effectively discriminate between these options, the endolysosomal system employs complex regulatory strategies that crucially rely on reversible post-translational modifications (PTMs) with ubiquitin (Ub) and ubiquitin-like (Ubl) proteins. The cycle of conjugation, recognition and removal of different Ub-and Ubl-modified states informs cellular protein stability and behavior at spatial and temporal resolution and is thus well suited to finetune macromolecular complex assembly and function on endolysosomal membranes. Here, we discuss how ubiquitylation (also known as ubiquitination) and its biochemical relatives orchestrate endocytic traffic and designate cargo fate, influence membrane identity transitions and support formation of membrane contact sites (MCSs). Finally, we explore the opportunistic hijacking of Ub and Ubl modification cascades by intracellular bacteria that remodel host trafficking pathways to invade and prosper inside cells. Show less
A human consists of billions of cells. All these cells need to know in which organ they are located and what their position inside the organ is. One way to obtain this information is via morphogens... Show moreA human consists of billions of cells. All these cells need to know in which organ they are located and what their position inside the organ is. One way to obtain this information is via morphogens, small particles providing positional information. We quantitatively studied the transport of the morphogen Decapentaplegic (Dpp) in the __wing imaginal disc__ (the precursor of the wing) of fruit fly larvae. Certain cells in this disc produce Dpp, while others receive it and determine their position according to the Dpp concentration. To study Dpp transport we first developed a microscope able to follow single molecules in three dimensions in living tissue with high spatial and temporal accuracy. With this microscope we then studied the subcellular processes governing intracellular Dpp transport. We determined how long Dpp resides in different types of endosomes (a cellular compartment involved in transport). We also found that the movement of endosomes is too small to facilitate Dpp transport. Furthermore we found differences in the in- and outflow of Dpp in endosomes. This work is one of the first to quantitatively study intracellular morphogen transport. It provides new insights into growth and development of organisms. Show less
