The small GTP-binding protein rab4 controls an early sorting event on the endocytic pathway.
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.
van der Sluijs
P
P
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510.
Hull
M
M
Webster
P
P
Mâle
P
P
Goud
B
B
Mellman
I
I
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D004705:Endocytosis; D019204:GTP-Binding Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D014168:Transferrin / Q000378:metabolism; D020695:rab4 GTP-Binding Proteins
D009841:Oligonucleotides; D014168:Transferrin; D019204:GTP-Binding Proteins; D020695:rab4 GTP-Binding Proteins