A disease-associated mutation in the adhesion GPCR BAI2 (ADGRB2) increases receptor signaling activity.

ABSTRACT: Mutations in G protein-coupled receptors (GPCRs) that increase constitutive signaling activity can cause human disease. A de novo C-terminal mutation (R1465W) in the adhesion GPCR BAI2 (also known as ADGRB2) was identified in a patient suffering from progressive spastic paraparesis and other neurological symptoms. In vitro studies revealed that this mutation strongly increases the constitutive signaling activity of an N-terminally cleaved form of BAI2, which represents the activated form of the receptor. Further studies dissecting the mechanism(s) underling this effect revealed that wild-type BAI2 primarily couples to Gα_z , with the R1465W mutation conferring increased coupling to Gα_i . The R1465W mutation also increases the total and surface expression of BAI2. The m

SUBMITTER: Purcell RH 

PROVIDER: S-EPMC5679302 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature