Late endosomes derive from early endosomes by maturation

Cell. 1991 May 3;65(3):417-27. doi: 10.1016/0092-8674(91)90459-c.


Endocytosed proteins destined for degradation in lysosomes are targeted mainly to early endosomes following uptake. Late endosomes are the major site for entry of newly synthesized lysosomal hydrolases via the cation-independent mannose 6-phosphate receptor into the degradative pathway. No consensus exists as to the mechanism of transport from early to late endosomes. We used asialoorosomucoid and transferrin to label selected parts of the degradative and receptor-recycling pathways, respectively, in the human hepatoma cell line HepG2. Intracellular mixing of sequentially endocytosed 125I- and HRP-labeled ligands was monitored by using 3,3'-diaminobenzidine-mediated density perturbation. The entire endocytic pathway of asialoorosomucoid, except for the lysosomes, remained fully accessible to subsequently endocytosed transferrin conjugated to HRP with unchanged kinetics. These results together with immunoelectron microscopic data support a model in which early endosomes gradually mature into late endosomes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Asialoglycoproteins*
  • Cell Membrane / metabolism
  • Coated Pits, Cell-Membrane / metabolism
  • Coated Pits, Cell-Membrane / ultrastructure
  • Endocytosis*
  • Horseradish Peroxidase
  • Humans
  • Lysosomes / metabolism*
  • Lysosomes / ultrastructure
  • Mannosephosphates / metabolism
  • Microscopy, Immunoelectron
  • Models, Biological
  • Orosomucoid / analogs & derivatives
  • Orosomucoid / metabolism
  • Receptor, IGF Type 2
  • Receptors, Cell Surface / metabolism
  • Receptors, Transferrin / metabolism
  • Transferrin / metabolism
  • Tumor Cells, Cultured
  • Vacuoles / metabolism*
  • Vacuoles / ultrastructure


  • Asialoglycoproteins
  • Mannosephosphates
  • Orosomucoid
  • Receptor, IGF Type 2
  • Receptors, Cell Surface
  • Receptors, Transferrin
  • Transferrin
  • asialoorosomucoid
  • Horseradish Peroxidase