کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8321949 | 1539842 | 2018 | 31 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Assessing the real-time activation of the cannabinoid CB1 receptor and the associated structural changes using a FRET biosensor
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کلمات کلیدی
CREBERK1/2 MAP kinasePVDFkoffCB1GPCRscAMP - cAMPERK1/2 - ERK1 / 2G protein-coupled receptors - G گیرنده های پروتئینی همراهCyclic adenosine monophosphate - آدنوزین مونوفسفات CyclicFluorescence resonance energy transfer - انتقال انرژی رزونانس FluorescenceFRET - انتقال انرژی رزونانسی فورسترHuntington’s disease - بیماری هانتینگتونpolyvinylidene difluoride - دی فلوئورید پلی وینیلیدینtransmembrane - فرابنفشReceptor activation - فعال سازی گیرندهkon - می تواندG-proteins - پروتئین GcAMP-response element-binding protein - پروتئین متصل به عنصر cAMP-responseextracellular signal-regulated kinases 1 and 2 - کینازهای 1 و 2 تنظیم شده سیگنال خارج سلولیcannabinoid type 1 receptor - گیرنده نوع 1 کانابینوئیدcannabinoid receptor - گیرنده های کانابینوئیدG protein-coupled receptor - گیرندههای جفتشونده با پروتئین جی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The cannabinoid receptor 1 (CB1) is mainly expressed in the nervous system and regulates learning, memory processes, pain and energy metabolism. However, there is no way to directly measure its activation. In this study, we constructed a CB1 intramolecular fluorescence resonance energy transfer (FRET) sensor, which could measure CB1 activation by monitoring structural changes between the third intracellular loop and the C-terminal tail. CB1 agonists induced a time- and concentration-dependent increase in the FRET signal, corresponding to a reduction in the distance between the third intracellular loop and the C-terminal tail. This, in turn, mobilized intracellular Ca2+, inhibited cAMP accumulation, and increased phosphorylation of the ERK1/2 MAP kinases. The activation kinetics detected using this method were consistent with those from previous reports. Moreover, the increased FRET signal was markedly inhibited by the CB1 antagonist rimonabant, which also reduced phosphorylation of the ERK1/2 MAP kinases. We mutated a single cysteine residue in the sensor (at position 257 or 264) to alanine. Both mutation reduced the agonist-induced increase in FRET signal and structural changes in the CB1 receptor, which attenuated phosphorylation of the ERK1/2 MAP kinases. In summary, our sensor directly assesses the kinetics of CB1 activation in real-time and can be used to monitor CB1 structure and function.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 99, June 2018, Pages 114-124
Journal: The International Journal of Biochemistry & Cell Biology - Volume 99, June 2018, Pages 114-124
نویسندگان
Ying Liu, Lu-Yao Chen, Hong Zeng, Richard Ward, Nan Wu, Li Ma, Xi Mu, Qiu-Lan Li, Yang Yang, Su An, Xiao-Xi Guo, Qian Hao, Tian-Rui Xu,