Endolysosomal transport at the crossroads of cellular signaling

The endolysosomal system in eukaryotic cells regulates nutrient uptake and maintains the composition of the plasma membrane, among many other functions. In autophagy, it contributes not only to the cellular quality control system to remove damaged organelles, aggregates, and pathogens but also to cellular recycling of amino acids. Transport in the endolysosomal network relies on the correct identity of the involved organelles. Rab GTPases and lipid kinases provide this membrane identity on each organelle, thereby orchestrating the protein machinery for membrane fusion and fission. Dynamic exchange of identity markers provides the basis for adaptations of the endolysosomal system, which is closely linked to cellular nutrient signaling. Here, recent structural and functional insights into the regulation and interplay of Rab regulators, lipid kinases, and tethering complexes are reviewed, focusing on the model organism Saccharomyces cerevisiae.