Phosphorylation of β-arrestins impacts recruitment to Parathyroid Hormone Receptor 1 (PTH1R) at the cell surface and endosomes

Beta-arrestins 1 and 2 are intracellular proteins that regulate the location and signaling of GPCRs, including Parathyroid Hormone Receptor 1 (PTH1R). PTH1R triggers {beta}-arrestin-dependent signaling that may enhance bone formation. {beta}-arrestins can also be modified through phosphorylation, which influences their movement and signaling.

Researchers examined if phosphorylation of {beta}-arrestins affects their movement to the cell surface and early endosomes following PTH1R activation. Using specialized sensors and microscopic analysis, they measured the movement of {beta}-arrestins. They found that phosphorylation slightly alters plasma membrane movement, while it significantly reduces early endosome movement.

Both mutations reduced endosome movement, but the phosphomimetic mutation had a greater effect. Restoring specific phosphorylation sites in {beta}-arrestin 1 or 2 restored more endosome movement compared to other mutations. Dephosphorylation is necessary for PTH1R-stimulated {beta}-arrestin movement to early endosomes, with different sites impacted compared to other GPCRs.

These results suggest that {beta}-arrestins may be regulated differently by various stimuli, which could have implications for therapeutic targeting of {beta}-arrestin-dependent pathways.