Related Experiment Video
Updated: Aug 18, 2026

Brain Slice Biotinylation: An Ex Vivo Approach to Measure Region-specific Plasma Membrane Protein Trafficking in Adult Neurons
Published on: April 3, 2014
Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2
Wei Chen1, Xiu-Rong Ren, Christopher D Nelson
1Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. w.chen@duke.edu
Abstract:
Binding of Sonic Hedgehog (Shh) to Patched (Ptc) relieves the latter's tonic inhibition of Smoothened (Smo), a receptor that spans the cell membrane seven times. This initiates signaling which, by unknown mechanisms, regulates vertebrate developmental processes. We find that two molecules interact with mammalian Smo in an activation-dependent manner: G protein-coupled receptor kinase 2 (GRK2) leads to phosphorylation of Smo, and beta-arrestin 2 fused to green fluorescent protein interacts with Smo. These two processes promote endocytosis of Smo in clathrin-coated pits. Ptc inhibits association of beta-arrestin 2 with Smo, and this inhibition is relieved in cells treated with Shh. A Smo agonist stimulated and a Smo antagonist (cyclopamine) inhibited both phosphorylation of Smo by GRK2 and interaction of beta-arrestin 2 with Smo. beta-Arrestin 2 and GRK2 are thus potential mediators of signaling by activated Smo.
More Related Videos
Related Concept Videos
Cell Motility through Blebbing
Blebbing Through the Matrix
In multicellular...
Assembly of Signaling Complexes
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
TGF - β Signaling Pathway
Activation and Inactivation of G Proteins
GPCR Desensitization
IP3/DAG Signaling Pathway

