期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 215, 期 3, 页码 941-961出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20161714
关键词
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资金
- National Institutes of Health [F31 NS087801, F31 NS094004, F32 NS100461, R01NS045630, K23 NS084932, R01 NS079445]
- Muscular Dystrophy Association [293295]
- Edward J. Mallinckrodt, Jr. Foundation
- European Research Council
- Swiss National Science Foundation
- Clinical Research Priority Programs Small RNAs and Human Hemato-Lymphatic Diseases, SystemsX.ch (PrionX)
- Novartis Foundation
- Synapsis Foundation
- Clinical Research Priority Programs Small RNAs and Human Hemato-Lymphatic Diseases, SystemsX.ch (SynucleiX)
- European Union Seventh Framework Programme grant (NEURINOX)
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [R21HD075363] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR001412] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [F31NS087801, K23NS084932, F31NS094004, R01NS094164, R01NS045630, F32NS100461, R01NS079445] Funding Source: NIH RePORTER
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.
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