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GPR56/ADGRG1 regulates development and maintenance of peripheral myelin
Journal of Experimental Medicine ( IF 12.6 ) Pub Date : 2018-03-05 , DOI: 10.1084/jem.20161714
Sarah D Ackerman 1 , Rong Luo 2 , Yannick Poitelon 3 , Amit Mogha 1 , Breanne L Harty 1 , Mitchell D'Rozario 1 , Nicholas E Sanchez 1 , Asvin K K Lakkaraju 4 , Paul Gamble 5 , Jun Li 6, 7 , Jun Qu 6, 7 , Matthew R MacEwan 5, 8 , Wilson Zachary Ray 5, 8 , Adriano Aguzzi 4 , M Laura Feltri 3 , Xianhua Piao 9 , Kelly R Monk 10
Affiliation  

Myelin is a multilamellar sheath generated by specialized glia called Schwann cells (SCs) in the peripheral nervous system (PNS), which serves to protect and insulate axons for rapid neuronal signaling. In zebrafish and rodent models, we identify GPR56/ADGRG1 as a conserved regulator of PNS development and health. We demonstrate that, during SC development, GPR56-dependent RhoA signaling promotes timely radial sorting of axons. In the mature PNS, GPR56 is localized to distinct SC cytoplasmic domains, is required to establish proper myelin thickness, and facilitates organization of the myelin sheath. Furthermore, we define plectin—a scaffolding protein previously linked to SC domain organization, myelin maintenance, and a series of disorders termed “plectinopathies”—as a novel interacting partner of GPR56. Finally, we show that Gpr56 mutants develop progressive neuropathy-like symptoms, suggesting an underlying mechanism for peripheral defects in some human patients with GPR56 mutations. In sum, we define Gpr56 as a new regulator in the development and maintenance of peripheral myelin.



中文翻译:


GPR56/ADGRG1 调节外周髓磷脂的发育和维持



髓磷脂是由周围神经系统 (PNS) 中称为雪旺细胞 (SC) 的特殊神经胶质细胞产生的多层鞘,其作用是保护和隔离轴突,以实现快速神经元信号传导。在斑马鱼和啮齿动物模型中,我们将 GPR56/ADGRG1 确定为 PNS 发育和健康的保守调节因子。我们证明,在 SC 发育过程中,GPR56 依赖性 RhoA 信号传导促进轴突的及时径向排序。在成熟的 PNS 中,GPR56 定位于不同的 SC 细胞质结构域,需要建立适当的髓鞘厚度,并促进髓鞘的组织。此外,我们将 plectin(一种先前与 SC 结构域组织、髓磷脂维持和一系列称为“plectinopathies”的疾病相关的支架蛋白)定义为 GPR56 的新型相互作用伙伴。最后,我们发现Gpr56突变体会​​出现进行性神经病样症状,这表明一些GPR56突变人类患者外周缺陷的潜在机制。总之,我们将 Gpr56 定义为外周髓磷脂发育和维持的新调节因子。

更新日期:2018-03-06
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