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

Immunology and Cell Biology
Amanda C StanleyPaige Lacy

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 ...Continue Reading

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May 15, 2015·Cellular and Molecular Life Sciences : CMLS·Emiliano Panieri, Massimo M Santoro
Nov 12, 2014·Frontiers in Immunology·Rachael Zoe Murray, Jennifer Lea Stow
Oct 24, 2014·Frontiers in Immunology·Guillermo Arango Duque, Albert Descoteaux
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Apr 19, 2018·Antioxidants & Redox Signaling·Katrin Schröder
Jan 25, 2018·Cell Biology International·Priyadarshini BindalWen Lin Chai

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