Macropinocytosis: regulated coordination of endocytic and exocytic membrane traffic events

J Cell Sci. 2006 Nov 15;119(Pt 22):4758-69. doi: 10.1242/jcs.03238. Epub 2006 Oct 31.


Macropinocytosis, a form of bulk uptake of fluid and solid cargo into cytoplasmic vacuoles, called macropinosomes, has been studied mostly in relation to antigen presentation. Early membrane traffic events occurring in this process are, however, largely unknown. Using human dendritic cells we show that a marked increase in the rate of macropinocytosis occurs a few minutes after application of two markers (small latex beads or dextran), depends on a slow intracellular Ca2+ concentration ([Ca2+](i)) rise that precedes the PI3K-dependent step, and is preceded and accompanied by exocytosis of enlargeosomes compensating in part for the macropinocytic plasma membrane internalization. Unexpectedly, macropinosomes themselves, which share markers with endosomes, undergo Ca2+ -dependent exocytosis so that, after approximately 20 minutes of continuous bead or dextran uptake, an equilibrium is reached preventing cells from overloading themselves with the organelles. Large [Ca2+](i) increases induced by ionomycin trigger rapid (<1 minute) exocytic regurgitation of all macropinosomes, whereas endosomes remain apparently unaffected. We conclude that, in dendritic cells, the rate of macropinocytosis is not constant but increases in a regulated fashion, as previously shown in other cell types. Moreover, macropinosomes are not simple containers that funnel cargo to an endocytic pathway, but unique organelles, distinct from endosomes by their competence for regulated exocytosis and other membrane properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / physiology
  • Dendritic Cells / ultrastructure
  • Dextrans
  • Endocytosis / drug effects
  • Endocytosis / physiology*
  • Exocytosis / physiology*
  • Humans
  • Intracellular Membranes / drug effects
  • Intracellular Membranes / physiology*
  • Intracellular Membranes / ultrastructure
  • Ionomycin / pharmacology
  • Ionophores / pharmacology
  • Membrane Proteins / metabolism
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Microspheres
  • Phosphatidylinositol 3-Kinases / physiology
  • Pinocytosis / drug effects
  • Pinocytosis / physiology
  • Vesicular Transport Proteins / metabolism


  • Dextrans
  • Ionophores
  • Membrane Proteins
  • Vesicular Transport Proteins
  • early endosome antigen 1
  • Ionomycin
  • Phosphatidylinositol 3-Kinases
  • Calcium