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

In the peripheral nervous system, Schwann cell (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). The authors noticed biphasic roles of GPR126 which were governed by interactions with Laminin-211 – a novel ligand for GPR126 that modulates receptor signaling via a tethered agonist. The work suggests a model in which Laminin-211 mediates GPR126-induced cAMP levels to control early and late stages of SC development.