ERK1-Based Pathway as a New Selective Mechanism To Modulate CCR5 with Natural Antibodies

The Journal of Immunology : Official Journal of the American Association of Immunologists
Assunta VenutiLucia Lopalco

Abstract

Natural human Abs, recognizing an epitope within the first extramembrane loop of CCR5 (the main HIV coreceptor), induce a long-lasting internalization (48 h) of the protein, whereas all known CCR5 modulating molecules show a short-term kinetics (60-90 min). Despite extensive studies on the regulation of CCR5 signaling cascades, which are the effect of concomitant CCR5 internalization by exogenous stimuli such as Abs, downstream signaling continues to be poorly understood. In this article, we report a hitherto unrecognized mechanism of CCR5 modulation mediated by G protein-dependent ERK1 activity. We further demonstrate that ERK1 is localized mainly in the cytoplasmic compartment and that it interacts directly with the CCR5 protein, thus provoking possible CCR5 degradation with a subsequent de novo synthesis, and that re-expression of CCR5 on the cell membrane required several days. In contrast, the RANTES treatment induces a recovery of the receptor on the cell membrane in short-term kinetics without the involvement of de novo protein synthesis. The said new pathway could be relevant not only to better understand the molecular basis of all pathologic conditions in which CCR5 is involved but also to generate new tools to block v...Continue Reading

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Citations

Dec 23, 2016·Scientific Reports·Assunta VenutiLucia Lopalco
Aug 12, 2016·Scientific Reports·Gabriel SiracusanoMaria Teresa Sciortino
Nov 23, 2017·Frontiers in Immunology·Assunta VenutiLucia Lopalco
Aug 5, 2019·Cellular and Molecular Life Sciences : CMLS·Laura FantuzziLucia Lopalco
Dec 29, 2020·Trends in Pharmacological Sciences·Meredith A Skiba, Andrew C Kruse
Jun 2, 2020·Virus Research·Joel Henrique EllwangerJosé Artur Bogo Chies

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