The small GTP-binding protein rab4 controls an early sorting event on the endocytic pathway

Cell. 1992 Sep 4;70(5):729-40. doi: 10.1016/0092-8674(92)90307-x.


rab4 is a ras-like GTP-binding protein that associates with early endosomes in a cell cycle-dependent fashion. To determine its role during endocytosis, we generated stable cell lines that overexpressed mutant or wild-type rab4. By measuring endocytosis, transport to lysosomes, and recycling, we found that overexpression of wild-type rab4 had differential effects on the endocytic pathway. Although initial rates of internalization and degradation were not inhibited, the transfectants exhibited a 3-fold decrease in fluid phase endocytosis as well as an alteration in transferrin receptor (Tfn-R) recycling. Wild-type rab4 caused a redistribution of Tfn-R's from endosomes to the plasma membrane. It also blocked iron discharge by preventing the delivery of Tfn to acidic early endosomes, instead causing Tfn accumulation in a population of nonacidic vesicles and tubules. rab4 thus appears to control the function or formation of endosomes involved in recycling.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • CHO Cells
  • Cell Membrane / metabolism
  • Cricetinae
  • Endocytosis*
  • GTP-Binding Proteins / physiology*
  • Molecular Sequence Data
  • Oligonucleotides
  • Transferrin / metabolism
  • rab4 GTP-Binding Proteins


  • Oligonucleotides
  • Transferrin
  • GTP-Binding Proteins
  • rab4 GTP-Binding Proteins