Ligands for clathrin-mediated endocytosis are differentially sorted into distinct populations of early endosomes

Cell. 2006 Mar 10;124(5):997-1009. doi: 10.1016/j.cell.2005.12.038.


Cells rely on the correct sorting of endocytic ligands and receptors for proper function. Early endosomes have been considered as the initial sorting station where cargos for degradation separate from those for recycling. Using live-cell imaging to monitor individual endosomes and ligand particles in real time, we have discovered a sorting mechanism that takes place prior to early endosome entry. We show that early endosomes are in fact comprised of two distinct populations: a dynamic population that is highly mobile on microtubules and matures rapidly toward late endosomes and a static population that matures much more slowly. Several cargos destined for degradation are preferentially targeted to the dynamic endosomes, whereas the recycling ligand transferrin is nonselectively delivered to all early endosomes and effectively enriched in the larger, static population. This pre-early endosome sorting process begins at clathrin-coated vesicles, depends on microtubule-dependent motility, and appears to involve endocytic adaptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Cell Line
  • Cell Membrane / metabolism
  • Clathrin / metabolism*
  • Clathrin-Coated Vesicles / chemistry
  • Clathrin-Coated Vesicles / metabolism*
  • Endosomes / chemistry
  • Endosomes / metabolism*
  • Epidermal Growth Factor / metabolism
  • Fluorescent Dyes / metabolism
  • Hydrogen-Ion Concentration
  • Ligands*
  • Lipoproteins, LDL / metabolism
  • Microtubules / metabolism
  • Orthomyxoviridae / metabolism
  • Protein Transport / physiology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Transferrin / metabolism
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism
  • rab5 GTP-Binding Proteins / genetics
  • rab5 GTP-Binding Proteins / metabolism


  • Adaptor Proteins, Vesicular Transport
  • Clathrin
  • Fluorescent Dyes
  • Ligands
  • Lipoproteins, LDL
  • Recombinant Fusion Proteins
  • Transferrin
  • rab7 protein
  • Epidermal Growth Factor
  • rab GTP-Binding Proteins
  • rab5 GTP-Binding Proteins