Abstract
At least one of three receptor activity-modifying proteins (RAMP1, RAMP2 and RAMP3) can interact with 10 G protein-coupled receptors (GPCRs; nine Family B GPCRs and a Family C GPCR). All three RAMPs interact with the calcitonin (CT) receptor (CTR), the CTR-like receptor (CLR), the vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating polypeptide (PACAP) 1 (VPAC1) and the VPAC2 receptor, which are all Family B GPCRs. Three RAMPs enable CTR to function as three heterodimeric receptors for amylin, which is a feeding suppression peptide. These RAMPs also transport the CLR to the cell surface, where they function as a CT gene-related peptide (CGRP) receptor (CLR/RAMP1 heterodimer) and two adrenomedullin (AM) receptors (CLR/RAMP2 and CLR/RAMP3 heterodimers). CGRP and AM are potent hypotensive peptides that exert powerful protective effects against multi-organ damage. We recently reported that the third extracellular loop (ECL3) of CLR governs the activation of AM, but not CGRP, signaling in the three CLR/RAMP heterodimers. Furthermore, we showed that in the presence of RAMP2, the eighth helix (helix 8) in the proximal portion of the cytoplasmic C-terminal tail of the CLR, which is thought to be present in all family B GPCRs, participates in receptor signaling. In addition, we demonstrated that overexpression of GPCR kinase (GRK) 2, GRK3 and GRK4 enhances the AM-induced internalization of the CLR/RAMP2 heterodimer. In this review, we describe these studies and consider their implications for other Family B GPCRs that can interact with RAMPs.
Keywords: Receptor activity-modifying protein, calcitonin receptor-like receptor, calcitonin gene-related peptide, adrenomedullin, receptor activation, receptor internalization, G protein-coupled receptor kinase.
Current Protein & Peptide Science
Title:Functions of Third Extracellular Loop and Helix 8 of Family B GPCRs Complexed with RAMPs and Characteristics of their Receptor Trafficking
Volume: 14 Issue: 5
Author(s): Kenji Kuwasako, Debbie L Hay, Sayaka Nagata, Manabu Murakami, Kazuo Kitamura and Johji Kato
Affiliation:
Keywords: Receptor activity-modifying protein, calcitonin receptor-like receptor, calcitonin gene-related peptide, adrenomedullin, receptor activation, receptor internalization, G protein-coupled receptor kinase.
Abstract: At least one of three receptor activity-modifying proteins (RAMP1, RAMP2 and RAMP3) can interact with 10 G protein-coupled receptors (GPCRs; nine Family B GPCRs and a Family C GPCR). All three RAMPs interact with the calcitonin (CT) receptor (CTR), the CTR-like receptor (CLR), the vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating polypeptide (PACAP) 1 (VPAC1) and the VPAC2 receptor, which are all Family B GPCRs. Three RAMPs enable CTR to function as three heterodimeric receptors for amylin, which is a feeding suppression peptide. These RAMPs also transport the CLR to the cell surface, where they function as a CT gene-related peptide (CGRP) receptor (CLR/RAMP1 heterodimer) and two adrenomedullin (AM) receptors (CLR/RAMP2 and CLR/RAMP3 heterodimers). CGRP and AM are potent hypotensive peptides that exert powerful protective effects against multi-organ damage. We recently reported that the third extracellular loop (ECL3) of CLR governs the activation of AM, but not CGRP, signaling in the three CLR/RAMP heterodimers. Furthermore, we showed that in the presence of RAMP2, the eighth helix (helix 8) in the proximal portion of the cytoplasmic C-terminal tail of the CLR, which is thought to be present in all family B GPCRs, participates in receptor signaling. In addition, we demonstrated that overexpression of GPCR kinase (GRK) 2, GRK3 and GRK4 enhances the AM-induced internalization of the CLR/RAMP2 heterodimer. In this review, we describe these studies and consider their implications for other Family B GPCRs that can interact with RAMPs.
Export Options
About this article
Cite this article as:
Kuwasako Kenji, Hay L Debbie, Nagata Sayaka, Murakami Manabu, Kitamura Kazuo and Kato Johji, Functions of Third Extracellular Loop and Helix 8 of Family B GPCRs Complexed with RAMPs and Characteristics of their Receptor Trafficking, Current Protein & Peptide Science 2013; 14 (5) . https://dx.doi.org/10.2174/13892037113149990058
DOI https://dx.doi.org/10.2174/13892037113149990058 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Understanding eNOS for Pharmacological Modulation of Endothelial Function: A Translational View
Current Pharmaceutical Design Anti-Inflammatory Effects of Intravenous Anesthetics on Endotoxemia
Mini-Reviews in Medicinal Chemistry Traumatic Brain Injury: Preclinical Imaging Diagnostic(s) and Therapeutic Approaches
Current Pharmaceutical Design Innovative Therapeutic Strategies for Restoring Lymphocyte Functions in Septic Patients
Inflammation & Allergy - Drug Targets (Discontinued) Thromboxane Synthase Inhibitors and Thromboxane A2 Receptor Antagonists: A Quantitative Structure Activity Relationships (QSARs) Analysis
Current Medicinal Chemistry Management of Severe Abdominal Infections
Recent Patents on Anti-Infective Drug Discovery Bioactive Cyclohexenones: A Mini Review
Current Bioactive Compounds The Perfect Storm: A Rheumatologist's Point of View on COVID-19 Infection
Current Rheumatology Reviews Neuropeptide Mimetics and Antagonists in the Treatment of Inflammatory Disease: Focus on VIP and PACAP
Current Topics in Medicinal Chemistry Diamidine Activity Against Trypanosomes: The State of the Art
Current Molecular Pharmacology Respiratory Burns: A Clinical Review
Current Respiratory Medicine Reviews Editorial(Angiotensin II Receptor Research)
Current Pharmaceutical Design Hemothorax
Current Respiratory Medicine Reviews Statin Therapy
Current Pharmaceutical Design Cardioprotective effects of Aronia melanocarpa anthocynanins. From laboratory experiments to clinical practice.
Current Pharmaceutical Design Retraction Notice: Current Review of Ramosetron in the Prevention of Postoperative Nausea and Vomiting
Current Drug Safety Targeting <i>Plasmodium Metabolism</i> to Improve Antimalarial Drug Design
Current Protein & Peptide Science Therapeutic Modulation of Glutamate Receptors in Major Depressive Disorder
Current Neuropharmacology Contrast Agents in X-Ray Computed Tomography and Its Applications in Oncology
Anti-Cancer Agents in Medicinal Chemistry Heat Shock Protein Inhibitors for the Treatment of Fungal Infections
Recent Patents on Anti-Infective Drug Discovery