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FZD(5) is a G alpha(q)-coupled receptor that exhibits the functional hallmarks of prototypical GPCRs
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- Wright, Shane C. (författare)
- Karolinska Inst, Sect Receptor Biol & Signaling, Dept Physiol & Pharmacol, S-17165 Stockholm, Sweden;Univ Montreal, Inst Res Immunol & Canc, Dept Biochem & Mol Med, Montreal, PQ H3C 3J7, Canada
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- Canizal, Maria Consuelo Alonso (författare)
- Univ Wurzburg, Inst Pharmacol & Toxicol, Versbacher Str 9, D-97078 Wurzburg, Germany;Friedrich Schiller Univ Jena, Univ Hosp Jena, Inst Mol Cell Biol, Ctr Mol Biomed, Hans Knoll Str 2, D-07745 Jena, Germany
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- Benkel, Tobias (författare)
- Univ Bonn, Inst Pharmaceut Biol, D-53115 Bonn, Germany
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- (creator_code:org_t)
- AMER ASSOC ADVANCEMENT SCIENCE, 2018
- 2018
- Engelska.
- Ingår i: Science Signaling. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1945-0877 .- 1937-9145. ; 11:559
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- Frizzleds (FZDs) are a group of seven transmembrane-spanning (7TM) receptors that belong to class F of the G protein-coupled receptor (GPCR) superfamily. FZDs bind WNT proteins to stimulate diverse signaling cascades involved in embryonic development, stem cell regulation, and adult tissue homeostasis. Frizzled 5 (FZD(5)) is one of the most studied class F GPCRs that promote the functional inactivation of the beta-catenin destruction complex in response to WNTs. However, whether FZDs function as prototypical GPCRs has been heavily debated and, in particular, FZD(5) has not been shown to activate heterotrimeric G proteins. Here, we show that FZD(5) exhibited a conformational change after the addition of WNT-5A, which is reminiscent of class A and class B GPCR activation. In addition, we performed several live-cell imaging and spectrometric-based approaches, such as dual-color fluorescence recovery after photobleaching (dcFRAP) and resonance energy transfer (RET)-based assays that demonstrated that FZD(5) activated G alpha(q) and its downstream effectors upon stimulation with WNT-5A. Together, these findings suggest that FZD(5) is a 7TM receptor with a bona fide GPCR activation profile and suggest novel targets for drug discovery in WNT-FZD signaling.
Ämnesord
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
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