The Rho GTPase Rac1 is required for recycling endosome-mediated secretion of TNF in macrophages

Stanley, Amanda C., Wong, Colin X., Micaroni, Massimo, Venturato, Juliana, Khromykh, Tatiana, Stow, Jennifer L. and Lacy, Paige (2013) The Rho GTPase Rac1 is required for recycling endosome-mediated secretion of TNF in macrophages. Immunology and Cell Biology, 92 3: 275-286. doi:10.1038/icb.2013.90

Author Stanley, Amanda C.
Wong, Colin X.
Micaroni, Massimo
Venturato, Juliana
Khromykh, Tatiana
Stow, Jennifer L.
Lacy, Paige
Title The Rho GTPase Rac1 is required for recycling endosome-mediated secretion of TNF in macrophages
Journal name Immunology and Cell Biology   Check publisher's open access policy
ISSN 0818-9641
Publication date 2013-12-17
Year available 2013
Sub-type Article (original research)
DOI 10.1038/icb.2013.90
Open Access Status Not yet assessed
Volume 92
Issue 3
Start page 275
End page 286
Total pages 12
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 2403 Immunology
1307 Cell Biology
Abstract Rho GTPases are required for many cellular events such as adhesion, motility, and membrane trafficking. Here we show that in macrophages, the Rho GTPases Rac1 and Cdc42 are involved in lamellipodia and filopodia formation, respectively, and that both of these Rho GTPases are essential for the efficient surface delivery of tumor necrosis factor (TNF) to the plasma membrane following TLR4 stimulation. We have previously demonstrated intracellular trafficking of TNF via recycling endosomes in lipopolysaccharide (LPS)-activated macrophages. Here, we further define a specific role for Rac1 in intracellular TNF trafficking, demonstrating impairment in TNF release following TLR4 stimulation in the presence of a Rac inhibitor, in cells expressing a dominant negative (DN) form of Rac1, and following small interfering RNA (siRNA) knockdown of Rac1. Rac1 activity was required for TNF trafficking but not for TLR4 signaling following LPS stimulation. Reduced TNF secretion was due to a defect in Rac1 activity, but not of the closely related Rho GTPase Rac2, demonstrated by the additional use of macrophages derived from Rac2-deficient mice. Labeling recycling endosomes by the uptake of fluorescent transferrin enabled us to show that Rac1 was required for the final stages of TNF trafficking and delivery from recycling endosomes to the plasma membrane. Thus, actin remodeling by the Rho GTPase Rac1 is required for TNF cell surface delivery and release from macrophages.
Keyword Cytokine
Rho GTPase
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online ahead of print 17 December 2013.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
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Created: Fri, 24 Jan 2014, 01:46:27 EST by Susan Allen on behalf of Institute for Molecular Bioscience