Stressing endocytosis | Nature Cell Biology


Stressing endocytosis | Nature Cell Biology

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Access through your institution Buy or subscribe Rab proteins are involved in a multitude of membrane traffic and fusion events, including the endocytic pathway. They cycle between active


(GTP-bound) and inactive (GDP-bound), as well as between membrane-bound and cytosolic states. The latter cycle is regulated by RabGDI, which extracts GDP-bound Rab proteins from the


membrane, allowing their recycling to and subsequent activation at the next membrane. Both cycles are thought to ensure the directionality of membrane traffic. Cavalli _et al_. searched for


an upstream regulator of RabGDI that would increase its capacity to extract Rab5—a Rab protein involved in early steps of endocytic transport—from endosomal membranes. The activity they


identified was stress-activated p38 kinase, which directly phosphorylates serine 121 of RabGDI. In intact cells, the p38 pathway can be activated by various cellular stresses, such as


oxidative stress or UV irratiation. Under stress situations, Rab5 and its effector EEA1 were released from endosomes, and this depends on the presence of serine 121 in RabGDI. The image


shows that the association of EEA1 (red) with endosomes is resistant to H2O2-induced release in the presence of the RabGDI S121A mutant (co-transfected with a GFP construct (green) to label


transfected cells). Most importantly, exposure of cells to UV light or H2O2 increased the rate of endocytosis in normal cells but not in cells lacking p38. Furthermore, basal levels of p38


activity seem to be required for the basal rate of endocytosis. Taken together, these data point to the existence of a pathway that links p38 and RabGDI to both constitutive endocytic


membrane transport and its regulation in response to external stress stimuli. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your


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our FAQs * Contact customer support Authors * Barbara Marte View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and


permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Marte, B. Stressing endocytosis. _Nat Cell Biol_ 3, E92 (2001). https://doi.org/10.1038/35070154 Download citation * Issue Date: April 2001 *


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