Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

FPR2 signaling without β-… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

FPR2 signaling without β-arrestin recruitment alters the functional repertoire of neutrophils.

Artikel i vetenskaplig tidskrift
Författare Michael Gabl
André Holdfeldt
Martina Sundqvist
Jalal Lomei
Claes Dahlgren
Huamei Forsman
Publicerad i Biochemical pharmacology
ISSN 1873-2968
Publiceringsår 2017
Publicerad vid Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning
Språk en
Länkar dx.doi.org/10.1016/j.bcp.2017.08.01...
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Formyl peptide receptor Pepducin β-Arrestin Chemotaxis Biased agonism Desensitization Reactivation
Ämneskategorier Immunbiologi

Sammanfattning

G-protein coupled receptor (GPCR) biased agonism or functional selectivity has become an essential concept in GPCR research over the last years. Receptor-specific biased agonists selectively trigger one signaling pathway over another and induce a restricted/directed functional response. In this study, we aimed to characterize the concept of biased agonism for FPR2, a member of the formyl peptide receptor (FPR) subfamily of GPCRs. We show that the earlier described FPR2-activating pepducin F2Pal10 is a biased FPR2 agonist. The effects of F2Pal10 on neutrophil function differed in several aspects compared to those mediated by WKYMVM, a conventional FPR2-specific peptide agonist. Upon interaction with FPR2 expressed by neutrophils both F2Pal10 and WKYMVM activated the PLC-PIP2-Ca(2+) signaling pathway and the superoxide-generating NADPH-oxidase, but only WKYMVM activated the receptor to recruit β-arrestin. The functional consequences linked to a lack of β-arrestin recruitment were further explored, and we demonstrate that FPR2 desensitization occurred independent of β-arrestin. Despite this, reactivation of desensitized receptors achieved through a disruption of the cytoskeleton and through a novel FPR2 cross-talk mechanism with P2Y2R (the ATP receptor) and PAFR (the receptor for PAF) differed between F2Pal10-desensitized and WKYMVM-desensitized neutrophils. Further, the inability to recruit β-arrestin was found to be associated with a reduced rate of receptor internalization and impaired chemotaxis in neutrophils. In summary, we provide experimental evidence of biased agonism for FPR2 and our data disclose critical roles of β-arrestin in neutrophil chemotaxis and reactivation of desensitized receptors.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?