Gpr126 functions in schwann cells to control differentiation and myelination via G-protein activation

Amit Mogha, Andrew E. Benesh, Chinmoy Patra, Felix B. Engel, Torsten Schöneberg, Ines Liebscher, Kelly Monk

Research output: Contribution to journalArticle

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Abstract

The myelin sheath surrounding axons ensures that nerve impulses travel quickly and efficiently, allowing for the proper function of the vertebrate nervous system. We previously showed that the adhesion G-protein-coupled receptor (aGPCR) Gpr126 is essential for peripheral nervous system myelination, although the molecular mechanisms by which Gpr126 functions were incompletely understood. aGPCRs are a significantly understudied protein class, and it was unknown whether Gpr126 couples to G-proteins. Here, we analyze DhhCre;Gpr126fl/fl conditional mutants, and show that Gpr126 functions in Schwann cells (SCs) for radial sorting of axons and myelination. Furthermore, we demonstrate that elevation of cAMP levels or protein kinase A activation suppresses myelin defects in Gpr126 mouse mutants and that cAMP levels are reduced in conditional Gpr126 mutant peripheral nerve. Finally, we show that GPR126 directly increases cAMP by coupling to heterotrimeric G-proteins. Together, these data support a model in which Gpr126 functions in SCs for proper development and myelination and provide evidence that these functions are mediated via G-protein-signaling pathways.

Original languageEnglish (US)
Pages (from-to)17976-17985
Number of pages10
JournalJournal of Neuroscience
Volume33
Issue number46
DOIs
StatePublished - Nov 15 2013
Externally publishedYes

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Schwann Cells
Myelin Sheath
GTP-Binding Proteins
Axons
Heterotrimeric GTP-Binding Proteins
Peripheral Nervous System
G-Protein-Coupled Receptors
Cyclic AMP-Dependent Protein Kinases
Peripheral Nerves
Nervous System
Action Potentials
Vertebrates
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Gpr126 functions in schwann cells to control differentiation and myelination via G-protein activation. / Mogha, Amit; Benesh, Andrew E.; Patra, Chinmoy; Engel, Felix B.; Schöneberg, Torsten; Liebscher, Ines; Monk, Kelly.

In: Journal of Neuroscience, Vol. 33, No. 46, 15.11.2013, p. 17976-17985.

Research output: Contribution to journalArticle

Mogha, Amit ; Benesh, Andrew E. ; Patra, Chinmoy ; Engel, Felix B. ; Schöneberg, Torsten ; Liebscher, Ines ; Monk, Kelly. / Gpr126 functions in schwann cells to control differentiation and myelination via G-protein activation. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 46. pp. 17976-17985.
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