The LTB₄-BLT1 axis regulates the polarized trafficking of chemoattractant GPCRs during neutrophil chemotaxis.

ABSTRACT: Neutrophils sense and respond to diverse chemotactic cues through G-protein-coupled receptors (GPCRs). However, the precise trafficking dynamics of chemoattractant GPCRs during neutrophil activation and chemotaxis remain unclear. Here, by using small-molecule inhibitors and CRISPR-based knockouts, we establish that two primary chemoattractant GPCRs - formyl peptide receptor 1 (FPR1) and complement component 5a (C5a) receptor 1 (C5aR1) - internalize in a CDC42-actin-dependent manner. Through live-cell imaging, we demonstrate that, upon stimulation, FPR1 rapidly clusters and re-distributes along the plasma membrane to the trailing edge, where it internalizes and is directionally trafficked towards the front of migrating primary human neutrophils. In contrast to FPR1 and C5aR1, the leukotrien

SUBMITTER: Subramanian BC 

PROVIDER: S-EPMC6176921 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature