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Kinin B1 receptor h...
Kinin B1 receptor homo-oligomerization is required for receptor trafficking to the cell surface.
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- Sandén, Caroline (författare)
- Lund University,Lunds universitet,Drug Target Discovery,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Leeb-Lundberg, Fredrik (författare)
- Lund University,Lunds universitet,Drug Target Discovery,Forskargrupper vid Lunds universitet,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2013
- 2013
- Engelska.
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Ingår i: International Immunopharmacology. - : Elsevier BV. - 1878-1705 .- 1567-5769. ; 15:1, s. 121-128
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Abstract
Ämnesord
Stäng
- The kinin B1 receptor (B1R) is a G protein-coupled receptor with pro-inflammatory activity that is latent in healthy tissues but induced by tissue insult. Here, we investigated if B1R homo-oligomerization is a possible mechanism regulating the presentation of this receptor at the level of maturation and trafficking to the cell surface. To this end, we used HEK293 cells stably expressing N-terminal FLAG and HA epitope-tagged wild-type human B1R and an N-terminal receptor fragment, B1stop135, which terminates at the C-terminal end of the third transmembrane domain and has previously been shown to oligomerize with B1R. Receptors were monitored by immunoblotting and immunoprecipitation, receptor function by agonist binding and agonist-promoted phosphoinositide hydrolysis, and receptor trafficking by confocal immunofluorescence microscopy. When expressed alone, B1R is core N-glycosylated and forms oligomers localized intracellularly and on the cell surface. B1stop135 also exists as core N-glycosylated oligomers but is localized exclusively intracellularly. When co-expressed, B1stop135 prevents specifically B1R homo-oligomerization by forming nonfunctional B1R-B1stop135 hetero-oligomers, retains B1R intracellularly at least in part in the endoplasmatic reticulum (ER), increases calnexin binding to the receptor, and increases receptor degradation. We conclude that B1R homo-oligomerization is necessary for B1R maturation and trafficking to the cell surface. Modulating this mechanism may be a novel therapeutic avenue in inflammatory disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
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- ref (ämneskategori)
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