Fig. 10: Proposed model of the PTH-PTH1R-βarr2 complex assembly. | Nature Communications

Fig. 10: Proposed model of the PTH-PTH1R-βarr2 complex assembly.

From: Fast-diffusing receptor collisions with slow-diffusing peptide ligand assemble the ternary parathyroid hormone–GPCR–arrestin complex

Fig. 10

The receptor diffuses with near-Brownian motion until its collision with PTH which is temporarily retained at the cell surface by hyaluronic acid and randomly distributed (step 1). The PTH-bound-receptor has reduced diffusion and motion and induces PIP3 production at the plasma membrane (step 2), which in turn recruits βarr2 to the plasma membrane (step 3). The accumulation of the PTH-PTH1R-βarr2 complex in clathrin clusters can follow different pathways: a fast pathway where the larger accumulation of PIP3-recruited βarr2 in clathrin clusters interacts with the PTH-bound PTH1R in clathrin (steps 3 and 4, right); a slower pathway where βarr2 and PTH-PTH1R diffuse either as a complex or separately into nearby (<100 nm) clathrin spots (steps 3 and 4, left). Created in BioRender. Pacheco Romero, J. (2025) https://BioRender.com/u62m09.

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