Relaxin Family Peptides and Their Receptors

There are seven relaxin family peptides that are all structurally related to insulin. Relaxin has many roles in female and male reproduction, as a neuropeptide in the central nervous system, as a vasodilator and cardiac stimulant in the cardiovascular system, and as an antifibrotic agent. Insulin-like peptide-3 (INSL3) has clearly defined specialist roles in male and female reproduction, relaxin-3 is primarily a neuropeptide involved in stress and metabolic control, and INSL5 is widely distributed particularly in the gastrointestinal tract. Although they are structurally related to insulin, the relaxin family peptides produce their physiological effects by activating a group of four G protein-coupled receptors (GPCRs), relaxin family peptide receptors 1–4 (RXFP1–4). Relaxin and INSL3 are the cognate ligands for RXFP1 and RXFP2, respectively, that are leucine-rich repeat containing GPCRs. RXFP1 activates a wide spectrum of signaling pathways to generate second messengers that include cAMP and nitric oxide, whereas RXFP2 activates a subset of these pathways. Relaxin-3 and INSL5 are the cognate ligands for RXFP3 and RXFP4 that are closely related to small peptide receptors that when activated inhibit cAMP production and activate MAP kinases. Although there are still many unanswered questions regarding the mode of action of relaxin family peptides, it is clear that they have important physiological roles that could be exploited for therapeutic benefit.

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International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

Pharmacological Reviews ◽

10.1124/pr.114.009472 ◽

2015 ◽

Vol 67 (2) ◽

pp. 389-440 ◽

Cited By ~ 81

Author(s):

Michelle L. Halls ◽

Ross A. D. Bathgate ◽

Steve W. Sutton ◽

Thomas B. Dschietzig ◽

Roger J. Summers

Keyword(s):

Clinical Pharmacology ◽

Peptide Receptors ◽

International Union ◽

Recent Advances ◽

Relaxin Family ◽

Relaxin Family Peptides

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Multiple Binding Sites Revealed by Interaction of Relaxin Family Peptides with Native and Chimeric Relaxin Family Peptide Receptors 1 and 2 (LGR7 and LGR8)

Journal of Pharmacology and Experimental Therapeutics ◽

10.1124/jpet.104.080655 ◽

2005 ◽

Vol 313 (2) ◽

pp. 677-687 ◽

Cited By ~ 80

Author(s):

Michelle L. Halls ◽

Courtney P. Bond ◽

Satoko Sudo ◽

Jin Kumagai ◽

Tania Ferraro ◽

...

Keyword(s):

Binding Sites ◽

Peptide Receptors ◽

Multiple Binding Sites ◽

Relaxin Family ◽

Multiple Binding ◽

Relaxin Family Peptides

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The A-chain of Human Relaxin Family Peptides Has Distinct Roles in the Binding and Activation of the Different Relaxin Family Peptide Receptors

Journal of Biological Chemistry ◽

10.1074/jbc.m801911200 ◽

2008 ◽

Vol 283 (25) ◽

pp. 17287-17297 ◽

Cited By ~ 70

Author(s):

Mohammed Akhter Hossain ◽

K. Johan Rosengren ◽

Linda M. Haugaard-Jönsson ◽

Soude Zhang ◽

Sharon Layfield ◽

...

Keyword(s):

Peptide Receptors ◽

Relaxin Family ◽

A Chain ◽

Relaxin Family Peptides

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Neural Stem Cells: What Happens When They Go Viral?

Viruses ◽

10.3390/v13081468 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1468

Author(s):

Yashika S. Kamte ◽

Manisha N. Chandwani ◽

Alexa C. Michaels ◽

Lauren A. O’Donnell

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Viral Infections ◽

Wide Spectrum ◽

Cell Types ◽

Developmental Abnormalities ◽

Multipotent Progenitor Cells ◽

The Central Nervous System ◽

Simplex Virus ◽

The Brain

Viruses that infect the central nervous system (CNS) are associated with developmental abnormalities as well as neuropsychiatric and degenerative conditions. Many of these viruses such as Zika virus (ZIKV), cytomegalovirus (CMV), and herpes simplex virus (HSV) demonstrate tropism for neural stem cells (NSCs). NSCs are the multipotent progenitor cells of the brain that have the ability to form neurons, astrocytes, and oligodendrocytes. Viral infections often alter the function of NSCs, with profound impacts on the growth and repair of the brain. There are a wide spectrum of effects on NSCs, which differ by the type of virus, the model system, the cell types studied, and the age of the host. Thus, it is a challenge to predict and define the consequences of interactions between viruses and NSCs. The purpose of this review is to dissect the mechanisms by which viruses can affect survival, proliferation, and differentiation of NSCs. This review also sheds light on the contribution of key antiviral cytokines in the impairment of NSC activity during a viral infection, revealing a complex interplay between NSCs, viruses, and the immune system.

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Mild Clinical Presentation of Joubert Syndrome in a Male Adult Carrying Biallelic MKS1 Truncating Variants

Diagnostics ◽

10.3390/diagnostics11071218 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1218

Author(s):

Raffaella Brunetti-Pierri ◽

Marianthi Karali ◽

Francesco Testa ◽

Gerarda Cappuccio ◽

Maria Elena Onore ◽

...

Keyword(s):

Wide Spectrum ◽

Clinical Manifestations ◽

Brain Magnetic Resonance Imaging ◽

Joubert Syndrome ◽

Male Adult ◽

Full Field ◽

Pathogenic Variants ◽

Disease Spectrum ◽

Male Individual ◽

The Central Nervous System

Pathogenic variants in the MKS1 gene are responsible for a ciliopathy with a wide spectrum of clinical manifestations ranging from Meckel and Joubert syndrome (JBTS) to Bardet-Biedl syndrome, and involving the central nervous system, liver, kidney, skeleton, and retina. We report a 39-year-old male individual presenting with isolated Retinitis Pigmentosa (RP), as assessed by full ophthalmological evaluation including Best-Corrected Visual Acuity measurements, fundus examination, Goldmann Visual Field test, and full-field Electroretinography. A clinical exome identified biallelic nonsense variants in MKS1 that prompted post-genotyping investigations for systemic abnormalities of ciliopathy. Brain magnetic resonance imaging revealed malformations of the posterior cranial fossa with the ‘molar tooth sign’ and cerebellar folia dysplasia, which are both distinctive features of JBTS. No other organ or skeletal abnormalities were detected. This case illustrates the power of clinical exome for the identification of the mildest forms of a disease spectrum, such as a mild JBTS with RP in the presented case of an individual carrying biallelic truncating variants in MKS1.

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Mice with mutations in Trpm1, a gene in the locus of 15q13.3 microdeletion syndrome, display pronounced hyperactivity and decreased anxiety-like behavior

Molecular Brain ◽

10.1186/s13041-021-00749-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Tesshu Hori ◽

Shohei Ikuta ◽

Satoko Hattori ◽

Keizo Takao ◽

Tsuyoshi Miyakawa ◽

...

Keyword(s):

Visual Impairment ◽

Wide Spectrum ◽

Genetic Disorder ◽

Mutant Mice ◽

Chromosome 15 ◽

Microdeletion Syndrome ◽

Visual Transduction ◽

The Central Nervous System ◽

Null Mutant Mice

AbstractThe 15q13.3 microdeletion syndrome is a genetic disorder characterized by a wide spectrum of psychiatric disorders that is caused by the deletion of a region containing 7 genes on chromosome 15 (MTMR10, FAN1, TRPM1, MIR211, KLF13, OTUD7A, and CHRNA7). The contribution of each gene in this syndrome has been studied using mutant mouse models, but no single mouse model recapitulates the whole spectrum of human 15q13.3 microdeletion syndrome. The behavior of Trpm1−/− mice has not been investigated in relation to 15q13.3 microdeletion syndrome due to the visual impairment in these mice, which may confound the results of behavioral tests involving vision. We were able to perform a comprehensive behavioral test battery using Trpm1 null mutant mice to investigate the role of Trpm1, which is thought to be expressed solely in the retina, in the central nervous system and to examine the relationship between TRPM1 and 15q13.3 microdeletion syndrome. Our data demonstrate that Trpm1−/− mice exhibit abnormal behaviors that may explain some phenotypes of 15q13.3 microdeletion syndrome, including reduced anxiety-like behavior, abnormal social interaction, attenuated fear memory, and the most prominent phenotype of Trpm1 mutant mice, hyperactivity. While the ON visual transduction pathway is impaired in Trpm1−/− mice, we did not detect compensatory high sensitivities for other sensory modalities. The pathway for visual impairment is the same between Trpm1−/− mice and mGluR6−/− mice, but hyperlocomotor activity has not been reported in mGluR6−/− mice. These data suggest that the phenotype of Trpm1−/− mice extends beyond that expected from visual impairment alone. Here, we provide the first evidence associating TRPM1 with impairment of cognitive function similar to that observed in phenotypes of 15q13.3 microdeletion syndrome.

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Multifaceted Approach to Resveratrol Bioactivity: Focus on Antioxidant Action, Cell Signaling and Safety

Oxidative Medicine and Cellular Longevity ◽

10.4161/oxim.3.2.11147 ◽

2010 ◽

Vol 3 (2) ◽

pp. 86-100 ◽

Cited By ~ 64

Author(s):

Peter Kovacic ◽

Ratnasamy Somanathan

Keyword(s):

Cell Signaling ◽

Red Wine ◽

Wide Spectrum ◽

Physiological Activity ◽

Protective Agent ◽

Multifaceted Approach ◽

Beneficial Effects ◽

Naturally Occurring ◽

The Central Nervous System ◽

Future Work

Resveratrol (RVT) is a naturally occurring trihydroxy stilbene that displays a wide spectrum of physiological activity. Its ability to behave therapeutically as a component of red wine has attracted wide attention. The phenol acts as a protective agent involving various body constituents. Most attention has been given to beneficial effects in insults involving cancer, aging, cardiovascular system, inflammation and the central nervous system. One of the principal modes of action appears to be as antioxidant. Other mechanistic pathways entail cell signaling, apoptosis and gene expression. There is an intriguing dichotomy in relation to pro-oxidant property. Also discussed are metabolism, receptor binding, rationale for safety and suggestions for future work. This is the first comprehensive review of RVT based on a broad, unifying mechanism.

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Relaxin Family Peptide Receptors RXFP3 and RXFP4

Encyclopedia of Signaling Molecules ◽

10.1007/978-1-4614-6438-9_583-1 ◽

2016 ◽

pp. 1-17

Author(s):

Martina Kocan ◽

Sheng Yu Ang ◽

Roger J. Summers

Keyword(s):

Peptide Receptors ◽

Relaxin Family

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Dystonia Management: What to Expect From the Future? The Perspectives of Patients and Clinicians Within DystoniaNet Europe

Frontiers in Neurology ◽

10.3389/fneur.2021.646841 ◽

2021 ◽

Vol 12 ◽

Author(s):

Marenka Smit ◽

Alberto Albanese ◽

Monika Benson ◽

Mark J. Edwards ◽

Holm Graessner ◽

...

Keyword(s):

Information Exchange ◽

Wide Spectrum ◽

Neurological Diseases ◽

Evidence Base ◽

Diagnostic Process ◽

Reference Network ◽

Novel Treatments ◽

European Reference Network ◽

Specialized Care ◽

The Central Nervous System

Improved care for people with dystonia presents a number of challenges. Major gaps in knowledge exist with regard to how to optimize the diagnostic process, how to leverage discoveries in pathophysiology into biomarkers, and how to develop an evidence base for current and novel treatments. These challenges are made greater by the realization of the wide spectrum of symptoms and difficulties faced by people with dystonia, which go well-beyond motor symptoms. A network of clinicians, scientists, and patients could provide resources to facilitate information exchange at different levels, share mutual experiences, and support each other's innovative projects. In the past, collaborative initiatives have been launched, including the American Dystonia Coalition, the European Cooperation in Science and Technology (COST—which however only existed for a limited time), and the Dutch DystonieNet project. The European Reference Network on Rare Neurological Diseases includes dystonia among other rare conditions affecting the central nervous system in a dedicated stream. Currently, we aim to broaden the scope of these initiatives to a comprehensive European level by further expanding the DystoniaNet network, in close collaboration with the ERN-RND. In line with the ERN-RND, the mission of DystoniaNet Europe is to improve care and quality of life for people with dystonia by, among other endeavors, facilitating access to specialized care, overcoming the disparity in education of medical professionals, and serving as a solid platform to foster international clinical and research collaborations. In this review, both professionals within the dystonia field and patients and caregivers representing Dystonia Europe highlight important unsolved issues and promising new strategies and the role that a European network can play in activating them.

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