GPR56/ADG RG1 regulates development and maintenance of peripheral myelin

Sarah D. Ackerman, Rong Luo, Yannick Poitelon, Amit Mogha, Breanne L. Harty, Mitchell D’Rozario, Nicholas E. Sanchez, Asvin K.K. Lakkaraju, Paul Gamble, Jun Li, Jun Qu, Matthew R. MacEwan, Wilson Zachary Ray, Adriano Aguzzi, M. Laura Feltri, Xianhua Piao, Kelly R. Monk . Journal of Experimental Medicine, Volume 215, Issue 3, 1 March 2018, Pages 941-961 Read More

Abstract

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/ADG RG1 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. © 2018 Ackerman et al.

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Posted on March 19, 2018
Posted in: Axon Injury & Repair, NeuroRestorative Therapy, Publications Authors: ,