TY - JOUR
T1 - Gpr126 functions in schwann cells to control differentiation and myelination via G-protein activation
AU - Mogha, Amit
AU - Benesh, Andrew E.
AU - Patra, Chinmoy
AU - Engel, Felix B.
AU - Schöneberg, Torsten
AU - Liebscher, Ines
AU - Monk, Kelly R.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
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U2 - 10.1523/JNEUROSCI.1809-13.2013
DO - 10.1523/JNEUROSCI.1809-13.2013
M3 - Article
C2 - 24227709
AN - SCOPUS:84887359255
SN - 0270-6474
VL - 33
SP - 17976
EP - 17985
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 46
ER -