Proximity based proteomics reveals Git1 as a regulator of Smoothened signaling.

ABSTRACT: The GPCR-like protein Smoothened (Smo) plays a pivotal role in the Hedgehog (Hh) pathway. To initiate Hh signaling, active Smo binds to and inhibits the catalytic subunit of PKA in the primary cilium, a process facilitated by G protein-coupled receptor kinase 2 (Grk2). However, the precise regulatory mechanisms underlying this process, as well as the events preceding and following Smo activation, remain poorly understood. To address this question, we leveraged the proximity labeling tool TurboID and conducted a time-resolved proteomic study of Smo-associated proteins over the course of Hh signaling activation. Our results not only confirmed previously reported Smo interactors but also uncovered new Smo-associated proteins. We characterized one of these new Smo interactors, Grk-interacting

SUBMITTER: Zhang J 

PROVIDER: S-EPMC11741329 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature