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
-
Fenoldopam in Cardiovascular Surgery: A Review
Vascular Disease Prevention (Discontinued) Neonatal Systemic Thrombosis: An Updated Overview
Current Vascular Pharmacology The Medical Complications of Anorexia Nervosa and Their Treatments
Current Women`s Health Reviews Neurologic Sequelae in Critical Illness: Evaluation and Outcomes
Current Respiratory Medicine Reviews Obesity, Metabolic Syndrome, Diabetes and Arterial Hypertension
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Is There Any Scientific Basis of Hawan to be Used in the Alzheimer’s Disease Prevention/Cure?
Current Traditional Medicine Maternal Sepsis 2010: Early Recognition and Aggressive Treatment with Early Goal Directed Therapy can Improve Maternal Outcomes
Current Women`s Health Reviews Adverse HBOC-Endothelial Dysfunction Synergism: A Possible Contributor to Adverse Clinical Outcomes?
Current Drug Discovery Technologies De novo Designed Lipopolysaccharide Binding Peptides: Structure Based Development of Antiendotoxic and Antimicrobial Drugs
Current Medicinal Chemistry Induction and Amelioration of Environmental Stress in Isolated Islets Until Transplantation
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Oxidative Stress in Tumor Angiogenesis - Therapeutic Targets
Current Pharmaceutical Design Organosulphur Compounds Induce Apoptosis and Cell Cycle Arrest in Cervical Cancer Cells via Downregulation of HPV E6 and E7 Oncogenes
Anti-Cancer Agents in Medicinal Chemistry Meet Our Associate Editor
Current Molecular Medicine Editorial [Hot Topic: Pain - Unmet Need and Emerging Targets & Therapies (Guest Editor: Sivaram Pillarisetti)]
CNS & Neurological Disorders - Drug Targets In vivo Phenotyping Methods: Cytochrome P450 Probes with Emphasis on the Cocktail Approach
Current Pharmaceutical Design Managing Side Effects on Ocular Surface Caused by Glaucoma Eye Drops
Current Medicinal Chemistry Natural Products Towards the Discovery of Potential Future Antithrombotic Drugs
Current Pharmaceutical Design Anthracyclines Still Prove Effective in Anticancer Therapy
Mini-Reviews in Medicinal Chemistry A Key Role for Connexin Hemichannels in Spreading Ischemic Brain Injury
Current Drug Targets Garlic for Cardiovascular Disease: Prevention or Treatment?
Current Pharmaceutical Design