How do chemokines navigate neutrophils to the target site: Dissecting the structural mechanisms and signaling pathways.
In: Cellular signalling, Jg. 54 (2019-02-01), S. 69-80
academicJournal
Zugriff:
Chemokines play crucial roles in combating microbial infection and initiating tissue repair by recruiting neutrophils in a timely and coordinated manner. In humans, no less than seven chemokines (CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8) and two receptors (CXCR1 and CXCR2) mediate neutrophil functions but in a context dependent manner. Neutrophil-activating chemokines reversibly exist as monomers and dimers, and their receptor binding triggers conformational changes that are coupled to G-protein and β-arrestin signaling pathways. G-protein signaling activates a variety of effectors including Ca 2+ channels and phospholipase C. β-arrestin serves as a multifunctional adaptor and is coupled to several signaling hubs including MAP kinase and tyrosine kinase pathways. Both G-protein and β-arrestin signaling pathways play important non-overlapping roles in neutrophil trafficking and activation. Functional studies have established many similarities but distinct differences for a given chemokine and between chemokines at the level of monomer vs. dimer, CXCR1 vs. CXCR2 activation, and G-protein vs. β-arrestin pathways. We propose that two forms of the ligand binding two receptors and activating two signaling pathways enables fine-tuned neutrophil function compared to a single form, a single receptor, or a single pathway. We summarize the current knowledge on the molecular mechanisms by which chemokine monomers/dimers activate CXCR1/CXCR2 and how these interactions trigger G-protein/β-arrestin-coupled signaling pathways. We also discuss current challenges and knowledge gaps, and likely advances in the near future that will lead to a better understanding of the relationship between the chemokine-CXCR1/CXCR2-G-protein/β-arrestin axis and neutrophil function.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Titel: |
How do chemokines navigate neutrophils to the target site: Dissecting the structural mechanisms and signaling pathways.
|
---|---|
Autor/in / Beteiligte Person: | Rajarathnam, K ; Schnoor, M ; Richardson, RM ; Rajagopal, S |
Zeitschrift: | Cellular signalling, Jg. 54 (2019-02-01), S. 69-80 |
Veröffentlichung: | Oxford : Elsevier Science Ltd ; <i>Original Publication</i>: Oxford ; New York : Pergamon Press, 1988-, 2019 |
Medientyp: | academicJournal |
ISSN: | 1873-3913 (electronic) |
DOI: | 10.1016/j.cellsig.2018.11.004 |
Schlagwort: |
|
Sonstiges: |
|