The Rab5 effector Rabankyrin-5 regulates and coordinates different endocytic mechanisms

PLoS Biol. 2004 Sep;2(9):E261. doi: 10.1371/journal.pbio.0020261. Epub 2004 Aug 24.


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 epithelial cells, this function is primarily restricted to the apical membrane. Rabankyrin-5 localises to large pinocytic structures underneath the apical surface of kidney proximal tubule cells, and its overexpression in polarised Madin-Darby canine kidney cells stimulates apical but not basolateral, non-clathrin-mediated pinocytosis. In demonstrating a regulatory role in endosome fusion and (macro)pinocytosis, our studies suggest that Rab5 regulates and coordinates different endocytic mechanisms through its effector Rabankyrin-5. Furthermore, its active role in apical pinocytosis in epithelial cells suggests an important function of Rabankyrin-5 in the physiology of polarised cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Androstadienes / pharmacology
  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cloning, Molecular
  • Dogs
  • Down-Regulation
  • Endocytosis / physiology*
  • Endosomes / metabolism
  • Enzyme Inhibitors / pharmacology
  • Epithelial Cells / cytology
  • Fibroblasts / metabolism
  • GTP Phosphohydrolases / chemistry
  • Gene Expression Regulation*
  • Humans
  • Inositol Phosphates / chemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Liposomes / metabolism
  • Mice
  • Microscopy, Confocal
  • Microscopy, Video
  • Movement
  • NIH 3T3 Cells
  • Pinocytosis
  • Plasmids / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA Interference
  • Recombinant Proteins / chemistry
  • Time Factors
  • Wortmannin
  • rab5 GTP-Binding Proteins / physiology*


  • Androstadienes
  • Enzyme Inhibitors
  • Inositol Phosphates
  • Intracellular Signaling Peptides and Proteins
  • Liposomes
  • Recombinant Proteins
  • GTP Phosphohydrolases
  • rab5 GTP-Binding Proteins
  • Wortmannin