GoLoco/GPR motif-dependent regulation of Rap1GAP1 by Gα_o is disrupted by Gα_o encephalopathy variants.

ABSTRACT: G protein-coupled receptors (GPCRs) that couple to Gα_i/o family members are major therapeutic targets. Among heterotrimeric G proteins, Gα_o is the most abundant Gα subunit in the brain, but the mechanistic pathways controlled by Gα_o have not been thoroughly established. Understanding Gα_o-mediated signaling pathways is especially critical given recent reports of a neurodevelopmental disorder (GNAO1 encephalopathy) associated with mutations in the Gα_o-encoding gene. To address this gap, we sought to uncover novel Gα_o effectors using a proximity-based proteomics screen in differentiated PC12 cells. Our analysis revealed a diverse set of potential Gα_o-GTP effector proteins, including a Rap1 GTPase-activating protein,

SUBMITTER: Momplaisir NL 

PROVIDER: S-EPMC12329598 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature