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Neuron. 2015 Feb 18;85(4):755-69. doi: 10.1016/j.neuron.2014.12.057.

The adhesion GPCR GPR126 has distinct, domain-dependent functions in Schwann cell development mediated by interaction with laminin-211.

Author information

  • 1Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 2Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • 3Institute of Biochemistry, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
  • 4Department of Biochemistry, University of Buffalo, The State University of New York, Buffalo, NY 14023, USA.
  • 5Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: xianhua.piao@childrens.harvard.edu.
  • 6Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: monkk@wustl.edu.

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.

PMID:
25695270
PMCID:
PMC4335265
DOI:
10.1016/j.neuron.2014.12.057
[PubMed - indexed for MEDLINE]
Free PMC Article
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