FIGURE 1: Effects of stress conditions on Clathrin-mediated endocytosis. Stress conditions can either promote (right side) or hamper (left side) endocytosis. Increased endocytosis, e.g. triggered by the stress-induced activation of the mitogen-activated protein kinase p38 that activates Rab5 by promoting the formation of GDI:Rab5 complexes, reduces the cell surface levels of transmembrane cargo proteins. This may, for example, restrict signaling from the plasma membrane or the transporter-mediated uptake of nutrients and/or enhance the endocytic uptake of specific protein-bound ligands. Conversely, downregulation of endocytosis will extend the residence time of signaling receptors and transporters at the cell surface, thereby promoting their activities (see text and other figures for details).