The adhesion GPCR Gpr56 regulates oligodendrocyte development via interactions with Gα12/13 and RhoA.
The adhesion GPCR Gpr56 regulates oligodendrocyte development via interactions with Gα12/13 and RhoA.
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DOI：
10.1038/ncomms7122
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发表时间：
2015-01-21
影响因子：
16.6
通讯作者：
Monk KR
中科院分区：
文献类型：
--
作者：
Ackerman SD;Garcia C;Piao X;Gutmann DH;Monk KR
在脊椎动物中枢神经系统中，髓鞘少突胶质细胞是有丝分裂后的细胞，来源于增殖性少突胶质前体细胞(OPC)。控制少突胶质细胞发育的分子机制尚不完全清楚，但最近的研究表明，G蛋白偶联受体(AGPCRs)的粘附类是髓鞘形成的重要调节因子。在这里，我们使用斑马鱼和小鼠模型来剖析aGPCRGpr56在少突胶质细胞发育中的功能。我们发现GPR56在少突胶质细胞发育的早期阶段就有表达。此外，我们观察到在GPR56斑马鱼突变体中，成熟少突胶质细胞数量和有髓轴突显著减少。这种减少是由于OPC增殖减少，而不是增加了细胞死亡或改变了神经前体分化潜能。最后，我们证明这些功能是由Gα12/13蛋白和Rho激活所介导的。综上所述，我们的数据证实Gpr56是少突胶质细胞发育的调节因子。
In the vertebrate central nervous system, myelinating oligodendrocytes are postmitotic and derive from proliferative oligodendrocyte precursor cells (OPCs). The molecular mechanisms that govern oligodendrocyte development are incompletely understood, but recent studies implicate the adhesion class of G protein-coupled receptors (aGPCRs) as important regulators of myelination. Here, we use zebrafish and mouse models to dissect the function of the aGPCR Gpr56 in oligodendrocyte development. We show that gpr56 is expressed during early stages of oligodendrocyte development. Additionally, we observe a significant reduction of mature oligodendrocyte number and of myelinated axons in gpr56 zebrafish mutants. This reduction results from decreased OPC proliferation, rather than increased cell death or altered neural precursor differentiation potential. Finally, we show that these functions are mediated by Gα12/13 proteins and Rho activation. Together, our data establish Gpr56 as a regulator of oligodendrocyte development.
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影响因子：
3
作者：
Colognato H;Tzvetanova ID
通讯作者：
Tzvetanova ID
影响因子：
11.4
作者：
Baron, W;Shattil, SJ;ffrench-Constant, C
通讯作者：
ffrench-Constant, C
影响因子：
64.8
作者：
Fuenfschilling, Ursula;Supplie, Lotti M.;Mahad, Don;Boretius, Susann;Saab, Aiman S.;Edgar, Julia;Brinkmann, Bastian G.;Kassmann, Celia M.;Tzvetanova, Iva D.;Moebius, Wiebke;Diaz, Francisca;Meijer, Dies;Suter, Ueli;Hamprecht, Bernd;Sereda, Michael W.;Moraes, Carlos T.;Frahm, Jens;Goebbels, Sandra;Nave, Klaus-Armin
通讯作者：
Nave, Klaus-Armin
影响因子：
11.4
作者：
Arac, Demet;Boucard, Antony A.;Bolliger, Marc F.;Nguyen, Jenna;Soltis, S. Michael;Suedhof, Thomas C.;Brunger, Axel T.
通讯作者：
Brunger, Axel T.
影响因子：
2.5
作者：
KIMMEL, CB;BALLARD, WW;SCHILLING, TF
通讯作者：
SCHILLING, TF