G protein-coupled receptors (GPCRs) are members of a large protein family that share common structural motifs, including seven transmembrane helices, and play pivotal roles in cell-to-cell communications and in the regulation of cell functions. GPR103 is an orphan GPCR that shows similarities with orexin, neuropeptide FF, and cholecystokinin receptors.
In humans, 26RFa/QRFP has been found to be an endogenous ligand for the orphan receptor, GPR103 and it is one of the RFamide peptides, which have been shown to exert important neuroendocrine, behavioural, sensory and autonomic functions.
All the information we have till know couldn’ be available if we didn’t know the evolution of this important proteins and the relative interactions, which were discovered recently to be important for the regulation of locomotor activity, sleep and these neuropeptides and receptors exert neuroprotective effect in Alzheimer’s Disease.
Anyway, there is a long way to be walked on, because there is a need of additional information, while studing the molecular evolution of these proteins and peptides.
What is the Molecular Evolution?
In the First chapter the readers can find all about this branch of science and the problems this branch had overcomed in order to bring to the scientific community the molecularisation of the evolution concepts.
In the following chapter to the readers is presented a descriptive overview of G-proteins and G-protein coupled receptor.
In the other chapters it is also presented 26RFA/QRFP and pyroglutamylated RFamide peptide receptor (QRFPR) molecular evolution, where it is described the molecular phylogeny and the functional implication. It is even shown the unique study regarding the presence on natural selection (positive or negative selection) during the evolution of QRFPRs in mammals and fish species.
In the end of the book are shown the recent important finding regarding the function and the role of QRFP and its receptor, together with the experimental approach applied to zebrafish and rodents.
Anyway, it is imperative to mention that all the available knowledge from experiments to these animals can be useful for the curation of disorders and other deseases like Alzheimer’s Disease, only if we could understand well their molecular evolution.
Table of Contents
1. MOLECULAR EVOLUTION
2. G PROTEIN COUPLED RECEPTORS
3. G-PROTEINS
4. RFAMIDE NEUROPEPTIDE FAMILY AND 26-AMINO ACID RESIDUE RFAMIDE PEPTIDE (26RFA/QRFP)
5. PYROGLUTAMYLATED RFAMIDE PEPTIDE RECEPTOR
6. SURPRISES FROM THE FASCINATING RESEARCH ON QRFP AND ITS RECEPTORS
7. CONCLUSIONS AND FUTURE DIRECTIONS
8. BIBLIOGRAPHY
Research Objectives and Themes
The primary objective of this monograph is to elucidate the molecular evolution, phylogenetic relationships, and functional roles of the pyroglutamylated RFamide peptide (26RFa/QRFP) and its cognate G protein-coupled receptor (QRFPR/GPR103) across the vertebrate lineage, while exploring their neuroprotective implications in Alzheimer’s Disease.
- Molecular evolution and phylogeny of the RFamide peptide family and G protein-coupled receptors.
- Functional characterization and biological actions of the QRFP/QRFPR system in various vertebrate species.
- Investigation of natural selection pressures and biochemical property conservation in receptor evolution.
- Experimental analysis of the role of QRFP signaling in regulating locomotor activity and sleep in zebrafish.
- Examination of the neuroprotective effects and heterodimerization of GPR103 with orexin receptors in the context of Alzheimer’s Disease.
Excerpt from the Book
Unity and diversity of the structure of 26RFa/QRFP in vertebrates
The 26-amino acid residue RFamide peptide, 26RFa/QRFP, was identified for the first time in the brain of an amphibian species (Chartrel et al. 2003). An antibody against the RFamide motif was used to screen peptide fractions purified from a brain extract of the European green frog (Rana esculenta).
After HPLC purification, the sequence of the isolated substance was analyzed by mass spectrometry MS/MS fragmentation; it turned out to be a 26-amino acid peptide possessing the RFamide motif at its C-terminus, namely VGTALGSLAEELNGYNRKKGGFSFRFamide. This neuropeptide had not been reported in any animals previously and was designated as 26RFa (Figure 7A; Chartrel et al. 2003).
The amino acid sequence of frog 26RFa was employed to identify the cDNA encoding the counterpart of 26RFa in rat and humans (Chartrel et al. 2003). Concurrently, two other research groups independently identified 26RFa/QRFP precursors using a bioinformatic approach in the rat, mouse, bovine, and human genomes and paired 26RFa/QRFP with a previously identified orphan G protein-coupled receptor (GPCR), GPR103, also known as AQ27 or SP9155 (Fukusumi et al. 2003, Jiang et al. 2003; Figure 7B).
Summary of Chapters
MOLECULAR EVOLUTION: This chapter provides an introduction to the foundations of molecular evolution as a scientific discipline, detailing its historical context and the transition from morphological studies to molecular analysis.
G PROTEIN COUPLED RECEPTORS: This chapter offers a descriptive overview of G protein-coupled receptors, focusing on their structural characteristics, signaling mechanisms, and significance as therapeutic targets.
G-PROTEINS: This chapter details the history, discovery, and functional classification of heterotrimeric G-proteins, highlighting their conserved roles across evolution and their involvement in various disease processes.
RFAMIDE NEUROPEPTIDE FAMILY AND 26-AMINO ACID RESIDUE RFAMIDE PEPTIDE (26RFA/QRFP): This chapter discusses the identification, classification, and molecular evolution of the RFamide neuropeptide family, specifically focusing on the structure and phylogeny of 26RFa/QRFP in vertebrates.
PYROGLUTAMYLATED RFAMIDE PEPTIDE RECEPTOR: This chapter examines the QRFPR, detailing its evolutionary conservation, positive selection sites, and the functional significance of its biochemical properties in different species.
SURPRISES FROM THE FASCINATING RESEARCH ON QRFP AND ITS RECEPTORS: This chapter presents recent findings on the role of QRFP in regulating sleep and locomotor activity in zebrafish, alongside its potential neuroprotective function in Alzheimer’s Disease.
CONCLUSIONS AND FUTURE DIRECTIONS: This chapter synthesizes the core findings of the monograph and proposes future research directions, particularly regarding experimental validation and the exploration of orthologs in protostomes.
BIBLIOGRAPHY: This section lists the comprehensive academic references and sources cited throughout the monograph.
Keywords
Molecular Evolution, G protein-coupled receptors, GPCR, RFamide, QRFP, 26RFa, QRFPR, GPR103, Orexin, Alzheimer’s Disease, Phylogeny, Natural Selection, Signal Transduction, Zebrafish, Locomotor Activity
Frequently Asked Questions
What is the primary scope of this work?
This monograph explores the molecular evolution and biological significance of the QRFP/QRFPR signaling system, tracing its presence from fish to mammals and investigating its role in physiology and disease.
Which central themes are addressed in this book?
The work focuses on the evolutionary conservation of receptor-ligand pairs, the bioinformatics of phylogenetic reconstruction, the role of natural selection, and the physiological impact of QRFP on sleep and neurological health.
What is the primary research question?
The work seeks to understand how the QRFP/QRFPR system evolved across vertebrate species and how its signaling mechanisms contribute to regulatory functions like sleep control and neuroprotection in Alzheimer's Disease.
What scientific methods are utilized?
The study employs a combination of comparative bioinformatics (phylogenetic trees, synteny analysis, selection pressure models), molecular biology techniques (qPCR, RT-PCR), and pharmacological experimental approaches (in vitro cell assays, heat shock-induced genetic models).
What is covered in the main body of the work?
The main body systematically progresses from the general principles of molecular evolution to the specific characterization of GPCRs and G-proteins, the identification of the RFamide family, and detailed comparative studies of the QRFPR system in diverse vertebrate taxa.
Which keywords characterize this work?
Key terms include molecular evolution, GPCR, QRFP, QRFPR, phylogeny, positive selection, sleep regulation, and Alzheimer’s Disease.
How does QRFP overexpression affect zebrafish?
Research indicates that overexpression of QRFP in zebrafish larvae significantly inhibits locomotor activity during light periods, suggesting a role for this neuropeptide in promoting sleep in diurnal vertebrates.
What is the neuroprotective role of QRFPR/GPR103 in Alzheimer's?
The research demonstrates that GPR103 forms functional heterodimers with orexin receptors, and that this system is downregulated in Alzheimer’s disease patients; restoring or maintaining this signaling is hypothesized to confer neuroprotective benefits.
- Quote paper
- Associate Professor Rigers Bakiu (Author), 2016, Molecular Evolution of Pyroglutamylated RFamide Peptide and Orphan G Protein Coupled Receptor, Munich, GRIN Verlag, https://www.grin.com/document/347085
