Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO.
Division of Newborn Medicine, Department of Medicine, Children's Hospital and Harvard Medical School, Boston, MA.
J Exp Med. 2018 Mar 5;215(3):941-961. doi: 10.1084/jem.20161714. Epub 2018 Jan 24.
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 mutants develop progressive neuropathy-like symptoms, suggesting an underlying mechanism for peripheral defects in some human patients with mutations. In sum, we define Gpr56 as a new regulator in the development and maintenance of peripheral myelin.
髓鞘是由特定的神经胶质细胞（Schwann 细胞）在周围神经系统（PNS）中产生的多层鞘，其作用是保护和隔离轴突，以实现快速的神经元信号传递。在斑马鱼和啮齿动物模型中，我们确定 GPR56/ADGRG1 是 PNS 发育和健康的保守调节因子。我们证明，在 Schwann 细胞发育过程中，GPR56 依赖的 RhoA 信号促进了轴突的适时放射状分选。在成熟的 PNS 中，GPR56 定位于 Schwann 细胞细胞质的特定区域，对于建立适当的髓鞘厚度和促进髓鞘鞘的组织排列是必需的。此外，我们将 previously linked to SC domain organization, myelin maintenance, and a series of disorders termed "plectinopathies"的连接蛋白-a 支架蛋白定义为 GPR56 的一个新的相互作用伙伴。最后，我们发现 突变体表现出进行性神经病变样症状，这表明一些人类 突变患者的外周缺陷的潜在机制。总之，我们将 Gpr56 定义为外周髓鞘发育和维持的一个新的调节因子。
