Open AccessNeutrophil Signaling That Challenges Dogmata of G Protein-Coupled Receptor Regulated Functions
Author(s) -
Cláes Dahlgren,
André Holdfeldt,
Simon Lind,
Jonas Mårtensson,
Michael Gabl,
Lena Björkman,
Martina Sundqvist,
Huamei Forsman
Publication year - 2020
Publication title -
acs pharmacology and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.271
H-Index - 10
ISSN - 2575-9108
DOI - 10.1021/acsptsci.0c00004
Subject(s) - g protein coupled receptor , heterotrimeric g protein , receptor , allosteric regulation , rhodopsin like receptors , biology , signal transduction , microbiology and biotechnology , chemotaxis , class c gpcr , g protein , computational biology , biochemistry , metabotropic receptor , agonist
Activation as well as recruitment of neutrophils, the most abundant leukocyte in human blood, to sites of infection/inflammation largely rely on surface-exposed chemoattractant receptors. These receptors belong to the family of 7-transmembrane domain receptors also known as G protein-coupled receptors (GPCRs) due to the fact that part of the downstream signaling relies on an activation of heterotrimeric G proteins. The neutrophil GPCRs share significant sequence homologies but bind many structurally diverse activating (agonistic) and inhibiting (antagonistic) ligands, ranging from fatty acids to purines, peptides, and lipopeptides. Recent structural and functional studies of neutrophil receptors have generated important information on GPCR biology in general; this knowledge aids in the overall understanding of general pharmacological principles, governing regulation of neutrophil function and inflammatory processes, including novel leukocyte receptor activities related to ligand recognition, biased/functional selective signaling, allosteric modulation, desensitization mechanisms and reactivation, and communication (cross-talk) between GPCRs. This review summarizes the recent discoveries and pharmacological hallmarks with focus on neutrophil GPCRs. In addition, unmet challenges are dealt with, including recognition by the receptors of diverse ligands and how biased signaling mediates different biological effects.