Figure 5.

Schema depicting proposed mechanism of CRFR1-mediated sensitization of 5-HT₂R signaling. (A) Agonist activation of CRFR1 leads to the β-arrestin and clathrin-dependent endocytosis of CRFR1. (B) CRFR1 is internalized to Rab5-positive endosomes, where it is colocalized with constitutively internalized 5-HT₂R. (C) The PDZ binding motifs of both CRFR1 and 5-HT₂Rs are required for the Rab4-positive rapid recycling endosome-dependent and CRFR1-facilitated recycling of internalized 5-HT₂R to the cell surface via a putative interaction with a PDZ domain containing protein. (D) Due to increased 5-HT₂R cell surface expression mediated by CRFR1 activation 5-HT₂R signalling is enhanced. H, hormone.