کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815130 | 1058451 | 2016 | 54 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Modulation of primary cilia length by melanin-concentrating hormone receptor 1
ترجمه فارسی عنوان
مدولاسیون طول ساقه اولیه توسط گیرنده هورمون متمرکز کننده ملانین 1
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کلمات کلیدی
smoothened agonistPKCPTXGSK3βMCHPI3KionomycinSMOSAGEpacβARKctIFTMelanin-concentrating hormone receptorAcTubMCHRC-tailSomatostatin 14TSABBSPGE2pKaGPCRERKcyclic AMP - AMP cycliccAMP - cAMPG-protein-coupled receptor - G-پروتئین گیرندهG-protein-coupled receptor (GPCR) - G-پروتئین گیرنده (GPCR)Small interfering RNA - RNA تداخل کوچکsiRNA - siRNAacetylated α-tubulin - α-توبولین آتریلت شدهTrichostatin A - تریکوستاتین Aintraflagellar transport - حمل داخل قطارC-terminal tail - دمپایی C-terminalAkt pathway - راه آکتpertussis toxin - سموم سورافنیBardet–Biedl syndrome - سندرم باردت-بیدلSmoothened - صافphosphoinositide 3-kinase - فسفینوزیتید 3-کینازmelanin-concentrating hormone - هورمون متمرکز کننده ملانینMelanin-concentrating hormone (MCH) - هورمون متمرکز کننده ملانین (MCH)Primary cilia - پرتوی اولیهG-protein - پروتئین GExchange protein directly activated by cAMP - پروتئین تبادل شده به طور مستقیم توسط cAMP فعال می شودprotein kinase A - پروتئین کیناز AProtein kinase C - پروتئین کیناز سیProstaglandin E2 - پروستاگلاندین E2extracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولیGlycogen synthase kinase 3β - گلیکوزین سنتاز کیناز 3β
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
چکیده انگلیسی
Melanin-concentrating hormone (MCH) receptor 1 (MCHR1) is a class A G-protein-coupled receptor (GPCR). The MCH-MCHR1 system has been implicated in the regulation of feeding, emotional processing, and sleep in rodents. Recent work revealed that MCHR1 is selectively expressed in neuronal primary cilia of the central nervous system. Cilia have various chemosensory functions in many types of cell, and ciliary dysfunction is associated with ciliopathies such as polycystic kidney disease and obesity. Although dynamic modulation of neuronal cilia length is observed in obese mice, the functional interaction of neuronal ciliary GPCR and its endogenous ligand has not yet been elucidated. We report here that MCH treatment significantly reduced cilia length in hTERT-RPE1 cells (hRPE1 cells) transfected with MCHR1. Quantitative analyses indicated that MCH-induced cilia shortening progressed in a dose-dependent manner with an EC50 lower than 1Â nM when cells were treated for 6Â h. Although the assembly and disassembly of primary cilia are tightly coupled to the cell cycle, cell cycle reentry was not a determinant of MCH-induced cilia shortening. We confirmed that MCH elicited receptor internalization, Ca2Â + mobilization, ERK and Akt phosphorylation, and inhibition of cyclic AMP accumulation in MCHR1-expressing hRPE1 cells. Among these diverse pathways, we revealed that Gi/o-dependent Akt phosphorylation was an important component in the initial stage of MCH-induced cilia length shortening. Furthermore, induction of fewer cilia by Kif3A siRNA treatment significantly decreased the MCH-mediated phosphorylation of Akt, indicating the functional importance of the MCHR1-Akt pathway in primary cilia. Taken together, the present data suggest that the MCH-MCHR1 axis may modulate the sensitivity of cells to external environments by controlling the cilia length. Therefore, further characterization of MCHR1 as a ciliary GPCR will provide a potential molecular mechanism to link cilia length control with obesity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 28, Issue 6, June 2016, Pages 572-584
Journal: Cellular Signalling - Volume 28, Issue 6, June 2016, Pages 572-584
نویسندگان
Akie Hamamoto, Shogo Yamato, Yohei Katoh, Kazuhisa Nakayama, Kentaro Yoshimura, Sen Takeda, Yuki Kobayashi, Yumiko Saito,