Cell. 1992 Sep 4;70(5):729-40.

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

van der Sluijs P, Hull M, Webster P, Mâle P, Goud B, Mellman I.

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Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510.

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.

PMID:: 1516131; [PubMed - indexed for MEDLINE]

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