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 Monk

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)941-961
Number of pages21
JournalJournal of Experimental Medicine
Volume215
Issue number3
DOIs
StatePublished - Mar 1 2018

Fingerprint

Myelin Sheath
Schwann Cells
Maintenance
Peripheral Nervous System
Axons
Plectin
Zebrafish
Neuroglia
Rodentia
Mutation
Health
Proteins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Ackerman, S. D., Luo, R., Poitelon, Y., Mogha, A., Harty, B. L., D'Rozario, M., ... Monk, K. (2018). GPR56/ADG RG1 regulates development and maintenance of peripheral myelin. Journal of Experimental Medicine, 215(3), 941-961. https://doi.org/10.1084/jem.20161714

GPR56/ADG RG1 regulates development and maintenance of peripheral myelin. / Ackerman, Sarah D.; Luo, Rong; Poitelon, Yannick; Mogha, Amit; Harty, Breanne L.; D'Rozario, Mitchell; Sanchez, Nicholas E.; Lakkaraju, Asvin K.K.; Gamble, Paul; Li, Jun; Qu, Jun; MacEwan, Matthew R.; Ray, Wilson Zachary; Aguzzi, Adriano; Feltri, M. Laura; Piao, Xianhua; Monk, Kelly.

In: Journal of Experimental Medicine, Vol. 215, No. 3, 01.03.2018, p. 941-961.

Research output: Contribution to journalArticle

Ackerman, SD, Luo, R, Poitelon, Y, Mogha, A, Harty, BL, D'Rozario, M, Sanchez, NE, Lakkaraju, AKK, Gamble, P, Li, J, Qu, J, MacEwan, MR, Ray, WZ, Aguzzi, A, Feltri, ML, Piao, X & Monk, K 2018, 'GPR56/ADG RG1 regulates development and maintenance of peripheral myelin', Journal of Experimental Medicine, vol. 215, no. 3, pp. 941-961. https://doi.org/10.1084/jem.20161714
Ackerman SD, Luo R, Poitelon Y, Mogha A, Harty BL, D'Rozario M et al. GPR56/ADG RG1 regulates development and maintenance of peripheral myelin. Journal of Experimental Medicine. 2018 Mar 1;215(3):941-961. https://doi.org/10.1084/jem.20161714
Ackerman, Sarah D. ; Luo, Rong ; Poitelon, Yannick ; Mogha, Amit ; Harty, Breanne L. ; D'Rozario, Mitchell ; Sanchez, Nicholas E. ; Lakkaraju, Asvin K.K. ; Gamble, Paul ; Li, Jun ; Qu, Jun ; MacEwan, Matthew R. ; Ray, Wilson Zachary ; Aguzzi, Adriano ; Feltri, M. Laura ; Piao, Xianhua ; Monk, Kelly. / GPR56/ADG RG1 regulates development and maintenance of peripheral myelin. In: Journal of Experimental Medicine. 2018 ; Vol. 215, No. 3. pp. 941-961.
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