Common GPCR Interacting Partners Sample Clauses

Common GPCR Interacting Partners. GPCR localization, pharmacology, and signal transduction, can be further fine-tuned by a variety of additional interacting partners (Xxxxxx and Xxxx 2009; Magalhaes, Dunn, and Xxxxxxxx 2012). Thus far, GPCR signaling has been discussed in terms of a single GPCR binding a ligand and interacting with intracellular effectors. However considerable evidence indicates GPCRs can form physical associations with other receptors (Bouvier 2001; Ferre et al. 2014; Bulenger, Marullo, and Bouvier 2005). Dimerization of duplicate (homodimerization) or unrelated receptors (heterodimerization) has been shown to affect receptor expression, trafficking, ligand binding, G protein coupling, downstream signaling and regulation (Xxxxxxxxx and Xxxxxxx 2004). Many examples of functional GPCR oligomers have been described, including the members of the Glutamate family (Kniazeff et al. 2011). GPCR interactions extend beyond formation of receptor pairs and oligomers. Interactions with PDZ proteins have been shown to affect receptor localization, stability, signaling, and regulation (Magalhaes, Dunn, and Xxxxxxxx 2012; Xxxx and Xxxxxxxx 2015). PDZ proteins contain one or more PDZ domains, named for the first three proteins in which they were discovered: Postsynaptic density protein 95, Discs large, and Zonula occludens protein 1. PDZ domains bind specific PDZ motifs at the extreme CT of interacting partners, including GPCRs. PDZ proteins often act as scaffolds, capable of tethering multiple proteins into complexes and modulating receptor function (Magalhaes, Dunn, and Xxxxxxxx 2012; Xxxx and Xxxxxxxx 2015). Receptor activity-modifying proteins (RAMPs) provide another important example of proteins that interact with GPCRs to modify their function. The RAMP family consists of three members, RAMP 1-3, which are single-pass transmembrane proteins with a large extracellular NT domain (McLatchie et al. 1998; Hay and Xxxxxxx 2016). RAMP proteins were discovered because of their integral role in calcitonin like receptor (CLR) biology. RAMPs are essential for CLR trafficking to the cell surface, and RAMP dimerization with CLR is necessary for ligand binding. Indeed, CLR agonist preference is determined by the associated RAMP– dimerization with RAMP1 forms the calcitonin gene- related peptide receptor while association with RAMP2 or 3 forms receptors for adrenomedullin (McLatchie et al. 1998; Xxxxxx et al. 2002). Although the function of RAMPs has been most extensively studied in regard to CLR ...