Identification of GPR83 as the receptor for the neuroendocrine peptide PEN.
Identification of GPR83 as the receptor for the neuroendocrine peptide PEN.
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DOI：
10.1126/scisignal.aad0694
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发表时间：
2016-04-26
影响因子：
7.3
通讯作者：
Devi LA
中科院分区：
文献类型：
--
作者：
Gomes I;Bobeck EN;Margolis EB;Gupta A;Sierra S;Fakira AK;Fujita W;Müller TD;Müller A;Tschöp MH;Kleinau G;Fricker LD;Devi LA
PEN是大脑中丰富的肽，与摄食调节有关。我们在小鼠下丘脑和Neuro2A细胞中鉴定了一种PEN受体。PEN结合并激活了G蛋白（异三聚体鸟嘌呤核苷酸结合蛋白）偶联受体GPR83。GPR83在小鼠脑和Neuro2A细胞中的表达减少减少了PEN的结合和信号传导，这与GPR83作为PEN的主要受体的功能一致。在某些脑区，GPR83与GPR171共定位，GPR171是一种结合神经肽bigLEN的GPCR， bigLEN是另一种参与摄食的神经肽，与PEN由相同的前体蛋白产生。这两种受体在细胞系中的共表达改变了每种受体的信号特性，表明它们之间存在功能上的相互作用。我们的数据证实了PEN是一种结合GPR83的神经肽，并提示这两个配体受体系统- PEN-GPR83和biglen - gpr171可能在功能上偶联调节摄食。
PEN is an abundant peptide in the brain that has been implicated in the regulation of feeding. We identified a receptor for PEN in mouse hypothalamus and Neuro2A cells. PEN bound to and activated GPR83, a G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptor (GPCR). Reduction of GPR83 expression in mouse brain and Neuro2A cells reduced PEN binding and signaling, consistent with GPR83 functioning as the major receptor for PEN. In some brain regions, GPR83 colocalized with GPR171, a GPCR that binds the neuropeptide bigLEN, another neuropeptide that is involved in feeding and is generated from the same precursor protein as is PEN. Coexpression of these two receptors in cell lines altered the signaling properties of each receptor, suggesting a functional interaction. Our data established PEN as a neuropeptide that binds GPR83 and suggested that these two ligand-receptor systems—PEN-GPR83 and bigLEN-GPR171—may be functionally coupled in the regulation of feeding.
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DOI：
10.2174/187152808786848360
发表时间：
2008-12-01
期刊：
Inflammation & Allergy Drug Targets
影响因子：
--
作者：
Hansen, Wiebke;Westendorf, Astrid M.;Buer, Jan
通讯作者：
Buer, Jan
影响因子：
7.3
作者：
Gupta, A.;Fujita, W.;Devi, L. A.
通讯作者：
Devi, L. A.
影响因子：
--
作者：
Fricker LD
通讯作者：
Fricker LD
影响因子：
15.9
作者：
Krashes, Michael J.;Koda, Shuichi;Lowell, Bradford B.
通讯作者：
Lowell, Bradford B.
影响因子：
2.9
作者：
Chakraborty, Tandra R.;Tkalych, Oleg;Salton, Stephen R. J.
通讯作者：
Salton, Stephen R. J.