the rab5 effector rabankyrin-5 regulates and coordinates different endocytic mechanismsrab5效应rabankyrin-5调节和协调不同的内吞作用的机制.pdfVIP

Open access, freely available online PLoS BIOLOGY The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms 1 2 3 4¤ 4 Carsten Schnatwinkel , Savvas Christoforidis , Margaret R. Lindsay , Sandrine Uttenweiler-Joseph , Matthias Wilm , 3 1* Robert G. Parton , Marino Zerial 1 Max-Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany, 2 Laboratory of Biological Chemistry, Medical School, University of Ioannina, Ioannina, Greece, 3 Institute for Molecular Bioscience, Centre for Microscopy and Microanalysis, School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia, 4 European Molecular Biology Laboratory, Heidelberg, Germany The small GTPase Rab5 is a key regulator of clathrin-mediated endocytosis. On early endosomes, within a spatially restricted domain enriched in phosphatydilinositol-3-phosphate [PI(3)P], Rab5 coordinates a complex network of effectors that functionally cooperate in membrane tethering, fusion, and organelle motility. Here we discovered a novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity. In addition to early endosomes, however, Rabankyrin-5 localises to large vacuolar structures that correspond to macropinosomes in epithelial cells and fibroblasts. Overexpression of Rabankyrin-5 increases the number of macropinosomes and stimulates fluid-phase uptake, whereas its downregulation inhibits these processes. In polarised epithe