The multilayered complexity of the chemokine receptor system

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D’Agostino, Gianluca and García-Cuesta, Eva María and Gomáriz, Rosa P. and Rodríguez-Frade, José Miguel and Mellado, Mario (2020) The multilayered complexity of the chemokine receptor system. Biochemical and Biophysical Research Communications, 528 (2). pp. 347-358. ISSN 0006-291X

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Official URL: https://doi.org/10.1016/j.bbrc.2020.02.120



Abstract

The chemokines receptor family are membrane-expressed class A-specific seven-transmembrane receptors linked to G proteins. Through interaction with the corresponding ligands, the chemokines, they induce a wide variety of cellular responses including cell polarization, movement, immune and inflammatory responses, as well as the prevention of HIV-1 infection. Like a Russian matryoshka doll, the chemokine receptor system is more complex than initially envisaged. This review focuses on the mechanisms that contribute to this dazzling complexity and how they modulate the signaling events triggered by chemokines. The chemokines and their receptors exist as monomers, dimers and oligomers, their expression pattern is highly regulated, and the ligands can bind distinct receptors with similar affinities. The use of novel imaging-based technologies, particularly real-time imaging modalities, has shed new light on the very dynamic conformations that chemokine receptors adopt depending on the cellular context, and that affect chemokine-mediated responses. This complex scenario presents both challenging and exciting opportunities for drug Discovery.


Item Type:Article
Uncontrolled Keywords:Chemokines; Chemokine receptors; Signaling; Dimerization; Oligomerization
Subjects:Medical sciences > Biology > Cytology
Medical sciences > Biology > Biochemistry
ID Code:64503
Deposited On:22 Mar 2021 09:42
Last Modified:22 Mar 2021 17:12

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