The expanding repertoire of receptor activity modifying protein (RAMP) function

Abstract

Receptor activity modifying proteins (RAMPs) associate with G-protein-coupled receptors (GPCRs) at the plasma membrane and together bind a variety of peptide ligands, serving as a communication interface between the extracellular and intracellular environments. The collection of RAMP-interacting GPCRs continues to expand and now consists of GPCRs from families A, B, and C, suggesting that RAMP activity is extremely prevalent. RAMP association with GPCRs can regulate GPCR function by altering ligand binding, receptor trafficking and desensitization, and downstream signaling pathways. Here, we elaborate on these RAMP-dependent mechanisms of GPCR regulation, which provide opportunities for pharmacological intervention.

Recycling of glucagon receptor to plasma membrane increases in adipocytes of obese rats by soy protein; implications for glucagon resistance

“…The steps in the lifecycle of GPCR include desensitization, endocytosis, internalization, resensitization, recycling, degradation and down‐regulation , and we propose that soy protein can modify some of these lifecycle processes of the GR in WAT. Christopoulos et al demonstrated that RAMP2 interacts with the GR , whereas Weston et al showed that this interaction increased both the ligand selectivity and G protein preference of the GR .…”

CGRP receptor activity in mice with global expression of human receptor activity modifying protein 1

“…In addition, this mouse may also facilitate studies on the biological role of the AMY 1 receptor in the biology and migraine pathogenesis of CGRP and possibly amylin. Finally, because RAMP1 is associated with multiple receptors, such as the VIP/PACAP receptors (Hay et al, ; Klein et al, ), these mice may also be useful for testing non‐CGRP‐based therapies. In conclusion, the global hRAMP1 mice may be useful for future development and screening of migraine therapeutic agents.…”

Beyond the Ligand: Extracellular and Transcellular G Protein–Coupled Receptor Complexes in Physiology and Pharmacology

“…However, GPCRs are increasingly found in complex with extracellular binding partners (Knapp and Wolfrum, 2016). One such example involves receptor activity-modifying proteins, which interact with both the transmembrane and extracellular domains of various GPCRs in cis to modulate signaling and trafficking processes by well established mechanisms (Hay and Pioszak, 2016;Klein et al, 2016). Intriguingly, recent studies have begun to identify additional GPCR interactions with secreted extracellular proteins, extracellular matrix (ECM) components, and adhesion molecules or multimeric complexes across cellular junctions, or transcellularly.…”