Type IV collagen is an activating ligand for the adhesion G protein-coupled receptor GPR126.
Type IV collagen is an activating ligand for the adhesion G protein-coupled receptor GPR126.
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DOI：
10.1126/scisignal.2005347
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发表时间：
2014-08-12
影响因子：
7.3
通讯作者：
Talbot WS
中科院分区：
文献类型：
--
作者：
Paavola KJ;Sidik H;Zuchero JB;Eckart M;Talbot WS
GPR126是一种罕见的异三聚体鸟嘌呤核苷酸结合蛋白（G蛋白）偶联受体（GPCR），对多种器官的发育至关重要。我们发现IV型胶原是基底膜的主要成分，与Gpr126结合并激活其信号功能。IV型胶原刺激啮齿动物雪旺细胞和表达外源性Gpr126的人胚胎肾293 （HEK 293）细胞产生环磷酸腺苷，雪旺细胞需要Gpr126活性才能分化。IV型胶原特异性结合到含有CUB和戊烷素结构域的Gpr126的细胞外n端区域。缺少整个n端区域的Gpr126衍生物具有组成性活性，表明该区域抑制信号传导，而配体结合减轻了这种抑制以刺激受体活性。一种新的斑马鱼突变，在CUB和戊素结构域破坏周围神经和内耳的发育后截断Gpr126。因此，我们的研究结果确定了IV型胶原作为GPR126的激活配体，确定了其激活机制，并强调了IV型胶原在基底膜中的先前未被认识的信号功能。
GPR126 is an orphan heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptor (GPCR) that is essential for the development of diverse organs. We found that type IV collagen, a major constituent of the basement membrane, binds to Gpr126 and activates its signaling function. Type IV collagen stimulates the production of cyclic adenosine monophosphate in rodent Schwann cells, which require Gpr126 activity to differentiate, and in human embryonic kidney 293 (HEK 293) cells expressing exogenous Gpr126. Type IV collagen specifically bound to the extracellular N-terminal region of Gpr126 containing the CUB and pentraxin domains. Gpr126 derivatives lacking the entire N-terminal region were constitutively active, suggesting that this region inhibits signaling, and that ligand binding relieves this inhibition to stimulate receptor activity. A new zebrafish mutation that truncates Gpr126 after the CUB and pentraxin domains disrupted development of peripheral nerves and the inner ear. Thus, our findings identify type IV collagen as an activating ligand for GPR126, define its mechanism of activation, and highlight a previously unrecognized signaling function of type IV collagen in basement membranes.
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DOI：
10.1242/dev.098061
发表时间：
2013-11
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Geng FS;Abbas L;Baxendale S;Holdsworth CJ;Swanson AG;Slanchev K;Hammerschmidt M;Topczewski J;Whitfield TT
通讯作者：
Whitfield TT
影响因子：
2.8
作者：
Cosgrove, D;Kornak, JM;Samuelson, G
通讯作者：
Samuelson, G
影响因子：
16.2
作者：
Cheng, LL;Mudge, AW
通讯作者：
Mudge, AW
影响因子：
4.4
作者：
Karpus, Olga N.;Veninga, Henrike;Hamann, Jorg
通讯作者：
Hamann, Jorg
影响因子：
7.8
作者：
CAREY, DJ;ELDRIDGE, CF;BUNGE, RP
通讯作者：
BUNGE, RP