GPI-anchored proteins are delivered to recycling endosomes via a distinct cdc42-regulated, clathrin-independent pinocytic pathway

Dev Cell. 2002 Apr;2(4):411-23. doi: 10.1016/s1534-5807(02)00145-4.


Endocytosis of cell-surface proteins via specific pathways is critical for their function. We show that multiple glycosylphosphatidylinositol-anchored proteins (GPI-APs) are endocytosed to the recycling endosomal compartment but not to the Golgi via a nonclathrin, noncaveolae mediated pathway. GPI anchoring is a positive signal for internalization into rab5-independent tubular-vesicular endosomes also responsible for a major fraction of fluid-phase uptake; molecules merely lacking cytoplasmic extensions are not included. Unlike the internalization of detergent-resistant membrane (DRM)-associated interleukin 2 receptor, endocytosis of DRM-associated GPI-APs is unaffected by inhibition of RhoA or dynamin 2 activity. Inhibition of Rho family GTPase cdc42, but not Rac1, reduces fluid-phase uptake and redistributes GPI-APs to the clathrin-mediated pathway. These results describe a distinct constitutive pinocytic pathway, specifically regulated by cdc42.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • COS Cells
  • Caveolae / metabolism
  • Clathrin / metabolism
  • Clathrin-Coated Vesicles / metabolism
  • Detergents
  • Endosomes / metabolism*
  • Glycosylphosphatidylinositols / metabolism*
  • Golgi Apparatus / metabolism
  • Green Fluorescent Proteins
  • Hydrogen-Ion Concentration
  • Indicators and Reagents / metabolism
  • Luminescent Proteins / metabolism
  • Pinocytosis / physiology*
  • Receptors, Interleukin-2 / metabolism
  • cdc42 GTP-Binding Protein / metabolism*
  • rab5 GTP-Binding Proteins / metabolism


  • Biomarkers
  • Clathrin
  • Detergents
  • Glycosylphosphatidylinositols
  • Indicators and Reagents
  • Luminescent Proteins
  • Receptors, Interleukin-2
  • Green Fluorescent Proteins
  • cdc42 GTP-Binding Protein
  • rab5 GTP-Binding Proteins