βArrestins: Ligand-directed regulators of 5-HT2A receptor trafficking and signaling events

Abstract

βArrestins are scaffolding and regulatory proteins that both modify and mediate G protein coupled receptor responsiveness by desensitizing G protein signaling pathways and facilitating receptor internalization and alternate downstream signaling cascades. This chapter details the studies that demonstrate a role for βarrestin2 in regulating 5-HT2A receptor responsiveness in vitro and in vivo. The studies presented herein demonstrate that while the 5-HT2A receptor is capable of being regulated through interactions with GRKs and βarrestins, interactions with other proteins can facilitate receptor desensitization and internalization through non-βarrestin-mediated mechanisms. Moreover, the pathways utilized for each of these events are determined by both the complement of intracellular proteins expressed in residence with the 5-HT2A receptor and the agonist acting at the receptor.