Cell
Volume 70, Issue 5, 4 September 1992, Pages 729-740
Journal home page for Cell

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

https://doi.org/10.1016/0092-8674(92)90307-XGet rights and content

Abstract

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.

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