The Adhesion GPCR GPR126 Has Distinct, Domain-Dependent Functions in Schwann Cell Development Mediated by Interaction with Laminin-211

Sarah C. Petersen, Rong Luo, Ines Liebscher, Stefanie Giera, Sung Jin Jeong, Amit Mogha, Monica Ghidinelli, M. Laura Feltri, Torsten Schöneberg, Xianhua Piao, Kelly Monk

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Myelin ensheathes axons to allow rapid propagation of action potentials and proper nervous system function. In the peripheral nervous system, Schwann cells(SCs) radially sort axons into a 1:1 relationship before wrapping an axonal segment to form myelin. SC myelination requires the adhesion G protein-coupled receptor GPR126, which undergoes autoproteolytic cleavage into an N-terminal fragment (NTF) and a seven-transmembrane-containing C-terminal fragment (CTF). Here we show that GPR126 has domain-specific functions in SC development whereby the NTF is necessary and sufficient for axon sorting, whereas the CTF promotes wrapping through cAMP elevation. These biphasic roles of GPR126 are governed by interactions with Laminin-211, which we define as a novel ligand for GPR126 that modulates receptor signaling via a tethered agonist. Our work suggests a model in which Laminin-211 mediates GPR126-induced cAMP levels to control early and late stages of SC development.

Original languageEnglish (US)
Pages (from-to)755-769
Number of pages15
JournalNeuron
Volume85
Issue number4
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Schwann Cells
Laminin
Axons
Myelin Sheath
Peripheral Nervous System
G-Protein-Coupled Receptors
Nervous System
Action Potentials
Ligands

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The Adhesion GPCR GPR126 Has Distinct, Domain-Dependent Functions in Schwann Cell Development Mediated by Interaction with Laminin-211. / Petersen, Sarah C.; Luo, Rong; Liebscher, Ines; Giera, Stefanie; Jeong, Sung Jin; Mogha, Amit; Ghidinelli, Monica; Feltri, M. Laura; Schöneberg, Torsten; Piao, Xianhua; Monk, Kelly.

In: Neuron, Vol. 85, No. 4, 01.01.2015, p. 755-769.

Research output: Contribution to journalArticle

Petersen, SC, Luo, R, Liebscher, I, Giera, S, Jeong, SJ, Mogha, A, Ghidinelli, M, Feltri, ML, Schöneberg, T, Piao, X & Monk, K 2015, 'The Adhesion GPCR GPR126 Has Distinct, Domain-Dependent Functions in Schwann Cell Development Mediated by Interaction with Laminin-211', Neuron, vol. 85, no. 4, pp. 755-769. https://doi.org/10.1016/j.neuron.2014.12.057
Petersen, Sarah C. ; Luo, Rong ; Liebscher, Ines ; Giera, Stefanie ; Jeong, Sung Jin ; Mogha, Amit ; Ghidinelli, Monica ; Feltri, M. Laura ; Schöneberg, Torsten ; Piao, Xianhua ; Monk, Kelly. / The Adhesion GPCR GPR126 Has Distinct, Domain-Dependent Functions in Schwann Cell Development Mediated by Interaction with Laminin-211. In: Neuron. 2015 ; Vol. 85, No. 4. pp. 755-769.
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