IL4/PGE{sub 2} induction of an enlarged early endosomal compartment in mouse macrophages is Rab5-dependent

Journal Article · Sat Jul 15 00:00:00 EDT 2006 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2006.03.025· OSTI ID:20857998

Wainszelbaum, Marisa J ^[1]; Proctor, Brandon M ^[1]; Pontow, Suzanne E ^[1]; Stahl, Philip D ^[1]; Barbieri, M Alejandro ^[1]

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1. Department of Cell Biology and Physiology, Washington University School of Medicine, 660 S. Euclid, Campus Box 8228, Saint Louis, MO 63110 (United States)

The endosomal compartment and the plasma membrane form a complex partnership that controls signal transduction and trafficking of different molecules. The specificity and functionality of the early endocytic pathway are regulated by a growing number of Rab GTPases, particularly Rab5. In this study, we demonstrate that IL4 (a Th-2 cytokine) and prostaglandin E{sub 2} (PGE{sub 2}) synergistically induce Rab5 and several Rab effector proteins, including Rin1 and EEA1, and promote the formation of an enlarged early endocytic (EEE) compartment. Endosome enlargement is linked to a substantial induction of the mannose receptor (MR), a well-characterized macrophage endocytic receptor. Both MR levels and MR-mediated endocytosis are enhanced approximately 7-fold. Fluid-phase endocytosis is also elevated in treated cells. Light microscopy and fractionation studies reveal that MR colocalizes predominantly with Rab5a and partially with Rab11, an endosomal recycling pathway marker. Using retroviral expression of Rab5a:S34N, a dominant negative mutant, and siRNA Rab5a silencing, we demonstrate that Rab5a is essential for the large endosome phenotype and for localization of MR in these structures. We speculate that the EEE is maintained by activated Rab5, and that the EEE phenotype is part of some macrophage developmental program such as cell fusion, a characteristic of IL4-stimulated cells.

• OSTI ID: 20857998
• Journal Information: Experimental Cell Research, Vol. 312, Issue 12; Other Information: DOI: 10.1016/j.yexcr.2006.03.025; PII: S0014-4827(06)00117-0; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
MACROPHAGES
MANNOSE
MICE
MUTANTS
PHENOTYPE
PROSTAGLANDINS
RECEPTORS
SPECIFICITY