scholarly journals The human non-visual opsin OPN3 regulates pigmentation of epidermal melanocytes through interaction with MC1R

2019 ◽  
Author(s):  
Rana N. Ozdeslik ◽  
Lauren E. Olinski ◽  
Melissa M. Trieu ◽  
Daniel D. Oprian ◽  
Elena Oancea
Keyword(s):  
Light Sensitivity ◽  
G Protein Coupled Receptors ◽  
Negative Regulator ◽  
Melanin Production ◽  
Melanocortin 1 Receptor ◽  
Skin Cells ◽  
Skin Physiology ◽  
Human Melanocytes ◽  
G Protein Coupled ◽  
The Brain

AbstractOpsins form a family of light-activated, retinal-dependent G-protein coupled receptors (GPCRs) that serve a multitude of visual and non-visual functions. Opsin3 (OPN3 or encephalopsin), initially identified in the brain, remains one of the few members of the mammalian opsin family with unknown function and ambiguous light-absorption properties. We recently discovered that OPN3 is highly expressed in human epidermal melanocytes—the skin cells that produce melanin. The melanin pigment is a critical defense against ultraviolet radiation and its production is mediated by the Gαs-coupled melanocortin-1 receptor (MC1R). The physiological function and light-sensitivity of OPN3 in melanocytes is yet to be determined. Here we show that in human epidermal melanocytes OPN3 acts as a negative regulator of melanin production by interacting with MC1R and modulating its cAMP signaling. OPN3 negatively regulates the cAMP response evoked by MC1R via activation of the Gαi subunit of G-proteins, thus decreasing cellular melanin levels. In addition to their functional relationship, OPN3 and MC1R colocalize at both the plasma membrane and in intracellular structures and form a physical complex. Remarkably, OPN3 can bind retinal, but does not mediate light-induced signaling in melanocytes. Our results identify a novel function for OPN3 in the regulation of the melanogenic pathway in epidermal melanocytes. Our results reveal a light-independent function for the poorly characterized OPN3 and a novel pathway that greatly expands our understanding of melanocyte and skin physiology.SignificanceOur data reveals a novel function for the non-visual opsin OPN3 in regulating the pigmentation of human melanocytes by interacting with and modulating the activity of MC1R.

scholarly journals Human nonvisual opsin 3 regulates pigmentation of epidermal melanocytes through functional interaction with melanocortin 1 receptor

2019 ◽  
Vol 116 (23) ◽  
pp. 11508-11517 ◽  
Author(s):  
Rana N. Ozdeslik ◽  
Lauren E. Olinski ◽  
Melissa M. Trieu ◽  
Daniel D. Oprian ◽  
Elena Oancea
Keyword(s):  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Light Sensitivity ◽  
Negative Regulator ◽  
Melanin Production ◽  
Melanocortin 1 Receptor ◽  
Skin Cells ◽  
Skin Physiology ◽  
G Protein Coupled ◽  
The Brain

Opsins form a family of light-activated, retinal-dependent, G protein-coupled receptors (GPCRs) that serve a multitude of visual and nonvisual functions. Opsin 3 (OPN3 or encephalopsin), initially identified in the brain, remains one of the few members of the mammalian opsin family with unknown function and ambiguous light absorption properties. We recently discovered that OPN3 is highly expressed in human epidermal melanocytes (HEMs)—the skin cells that produce melanin. The melanin pigment is a critical defense against ultraviolet radiation (UVR), and its production is mediated by the Gαs-coupled melanocortin 1 receptor (MC1R). The physiological function and light sensitivity of OPN3 in melanocytes are yet to be determined. Here, we show that in HEMs, OPN3 acts as a negative regulator of melanin production by modulating the signaling of MC1R. OPN3 negatively regulates the cyclic adenosine monophosphate (cAMP) response evoked by MC1R via activation of the Gαi subunit of G proteins, thus decreasing cellular melanin levels. In addition to their functional relationship, OPN3 and MC1R colocalize at both the plasma membrane and in intracellular structures, and can form a physical complex. Remarkably, OPN3 can bind retinal, but does not mediate light-induced signaling in melanocytes. Our results identify a function for OPN3 in the regulation of the melanogenic pathway in epidermal melanocytes; we have revealed a light-independent function for the poorly characterized OPN3 and a pathway that greatly expands our understanding of melanocyte and skin physiology.

scholarly journals The cell biology of smell

2010 ◽  
Vol 191 (3) ◽  
pp. 443-452 ◽  
Author(s):  
Shannon DeMaria ◽  
John Ngai
Keyword(s):  
Olfactory System ◽  
Cell Biology ◽  
Odorant Receptor ◽  
Large Family ◽  
G Protein Coupled Receptors ◽  
Odorant Receptors ◽  
Chemical Structures ◽  
Wide Range ◽  
G Protein Coupled ◽  
The Brain

The olfactory system detects and discriminates myriad chemical structures across a wide range of concentrations. To meet this task, the system utilizes a large family of G protein–coupled receptors—the odorant receptors—which are the chemical sensors underlying the perception of smell. Interestingly, the odorant receptors are also involved in a number of developmental decisions, including the regulation of their own expression and the patterning of the olfactory sensory neurons' synaptic connections in the brain. This review will focus on the diverse roles of the odorant receptor in the function and development of the olfactory system.

Transmembrane Signaling in the Brain by Serotonin, A Key Regulator of Physiology and Emotion

2005 ◽  
Vol 25 (5-6) ◽  
pp. 363-385 ◽  
Author(s):  
Tatyana Adayev ◽  
Buddima Ranasinghe ◽  
Probal Banerjee
Keyword(s):  
Gene Expression ◽  
Immune Cells ◽  
Functional Role ◽  
Living Organism ◽  
Covalent Modification ◽  
G Protein Coupled Receptors ◽  
And Behavior ◽  
G Protein Coupled ◽  
Compare And Contrast ◽  
The Brain

Serotonin (5-HT) is an ancient chemical that plays a crucial functional role in almost every living organism. It regulates platelet aggregation, activation of immune cells, and contraction of stomach and intestinal muscles. In addition, serotonin acts as a neurotransmitter in the brain and the peripheral nervous system. These activities are initiated by the binding of serotonin to 15 or more receptors that are pharmacologically classified into seven groups, 5-HT1 through 5-HT7. Each group is further divided into subgroups of receptors that are homologous but are encoded by discrete genes. With the exception of the 5-HT3 receptor-a cation channel—all of the others are G protein-coupled receptors that potentially activate or inhibit a large number of biochemical cascades. This review will endeavor to compare and contrast such signaling pathways with special attention to their tissue-specific occurrence, their possible role in immediate effects on covalent modification of other proteins, and relatively slower effects on gene expression, physiology and behavior.

Hematopoietic progenitor kinase 1 (HPK1) negatively regulates prostaglandin E2–induced fos gene transcription

Blood ◽  
2003 ◽  
Vol 101 (9) ◽  
pp. 3687-3689 ◽  
Author(s):  
Sansana Sawasdikosol ◽  
Kristin M. Russo ◽  
Steven J. Burakoff
Keyword(s):  
Prostaglandin E2 ◽  
G Protein ◽  
Gene Transcription ◽  
Ectopic Expression ◽  
G Protein Coupled Receptors ◽  
Negative Regulator ◽  
Critical Signal ◽  
Negative Regulatory Pathway ◽  
Expression Studies ◽  
G Protein Coupled

Prostaglandin E2 (PGE2) is the predominant eicosanoid product released by macrophages at the site of inflammation. Binding of PGE2 to its cognate 7 transmembrane-spanning G protein–coupled receptors (GPCRs) activates signaling pathways, leading to the synthesis of the Fos transcription factor. Because the Ste20 serine/threonine protein kinase (S/TPK) is a critical signal transducer for the G protein–coupled pheromone receptor in Saccharomyces cerevisiae, we postulated that the PGE2 GPCRs may activate one of the Ste20 mammalian orthologs. We demonstrate here that the catalytic activity of a hematopoietic cell–restricted, Ste20-related S/TPK, HPK1, is positively regulated by exposure to physiological concentrations of PGE2. Furthermore, ectopic expression studies implicated HPK1 as a negative regulator of PGE2-induced transcription of the fos gene. Our data suggest that PGE2-induced activation of HPK1 may represent a novel negative regulatory pathway capable of modulating PGE2-mediated gene transcription.

scholarly journals Effect of 5-hydroxytryptamine Receptor in the Lower Esophageal Sphincter Regulation Mechanism

2020 ◽  
Vol 3 (6) ◽  
Author(s):  
Hefei Li ◽  
Junfeng Liu ◽  
Xixuan Zhang ◽  
Zhiwei Lai ◽  
Zhen Gao ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Regulation Mechanism ◽  
Visceral Sensitivity ◽  
Gastrointestinal Dysfunction ◽  
Secretion Regulation ◽  
The Central Nervous System ◽  
Esophageal Sphincter ◽  
G Protein Coupled ◽  
The Brain

As a neurotransmitter and avascular active substance, the 5-hydroxytryptamine (5-HT, serotonin) is widely distributed in the central nervous system and surrounding tissues. The 5-HT can play its role by acting on its corresponding 5-HT receptor. Nowadays, the 5-HT receptor can be classified into seven, according to different signal transduction method of receptors, the 5-HT3 receptor belongs to the ligand-gated ion channels, while other six 5-HT receptors are involved into the G protein-coupled receptors and play the biological role by binding to specific G protein-coupled receptors (GPCRs) on the surface of the cell membrane. The 5-HT plays an important role in the brain-gut information transmission and studies showed that the physiological stimulations like having meals, and pathological stimulations like ischemia and stress could promote the release of the 5-HT. In the gastrointestinal tract, the 5-HT is closely related to gastrointestinal sensitivity, gastrointestinal movement and secretion regulation, as well as many gastrointestinal dysfunction disorders, such as gastrointestinal power and visceral sensitivity abnormality and abnormalities of brain-gut axis.

scholarly journals Melatonin

2002 ◽  
Vol 4 (1) ◽  
pp. 57-72 ◽  
Keyword(s):  
Seasonal Affective Disorder ◽  
Physiological Role ◽  
G Protein Coupled Receptors ◽  
The Body ◽  
Receptor Subtypes ◽  
Seasonal Breeding ◽  
Livestock Management ◽  
G Protein Coupled ◽  
The Brain ◽  
Melatonin Production

Melatonin (MEL) is a hormone synthesized and secreted by the pineal gland deep within the brain in response to photoperiodic cues relayed from the retina via an endogenous circadian oscillator within the suprachiasmatic nucleus in the hypothalamus. The circadian rhythm of melatonin production and release, characterized by nocturnal activity and daytime quiescence, is an important temporal signal to the body structures that can read it. Melatonin acts through high-affinity receptors located centrally and in numerous peripheral organs. Different receptor subtypes have been cloned and characterized: MT(1) and MT(2) (transmembrane G-protein-coupled receptors), and MT(3). However, their physiological role remains unelucidated, although livestock management applications already include the control of seasonal breeding and milk production. As for potential therapeutic applications, exogenous melatonin or a melatonin agonist and selective 5-hydroxytrypiamine receptor (5-HT(2c)) antagonist, eg, S 20098, can be used to manipulate circadian processes such as the sleep-vake cycle, which are frequently disrupted in many conditions, most notably seasonal affective disorder.

scholarly journals MOLECULAR EVOLUTION OF GPCRS: Melanocortin/melanocortin receptors

2014 ◽  
Vol 52 (3) ◽  
pp. T29-T42 ◽  
Author(s):  
Robert M Dores ◽  
Richard L Londraville ◽  
Jeremy Prokop ◽  
Perry Davis ◽  
Nathan Dewey ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Focal Point ◽  
Cartilaginous Fish ◽  
G Protein Coupled Receptors ◽  
Melanocortin Receptors ◽  
Accessory Proteins ◽  
Melanocortin 1 Receptor ◽  
Ligand Selectivity ◽  
G Protein Coupled ◽  
Receptor Accessory Protein

The melanocortin receptors (MCRs) are a family of G protein-coupled receptors that are activated by melanocortin ligands derived from the proprotein, proopiomelanocortin (POMC). During the radiation of the gnathostomes, the five receptors have become functionally segregated (i.e. melanocortin 1 receptor (MC1R), pigmentation regulation; MC2R, glucocorticoid synthesis; MC3R and MC4R, energy homeostasis; and MC5R, exocrine gland physiology). A focus of this review is the role that ligand selectivity plays in the hypothalamus/pituitary/adrenal–interrenal (HPA–I) axis of teleosts and tetrapods as a result of the exclusive ligand selectivity of MC2R for the ligand ACTH. A second focal point of this review is the roles that the accessory proteins melanocortin 2 receptor accessory protein 1 (MRAP1) and MRAP2 are playing in, respectively, the HPA–I axis (MC2R) and the regulation of energy homeostasis by neurons in the hypothalamus (MC4R) of teleosts and tetrapods. In addition, observations are presented on trends in the ligand selectivity parameters of cartilaginous fish, teleost, and tetrapod MC1R, MC3R, MC4R, and MC5R paralogs, and the modeling of the HFRW motif of ACTH(1–24) when compared with α-MSH. The radiation of the MCRs during the evolution of the gnathostomes provides examples of how the physiology of endocrine and neuronal circuits can be shaped by ligand selectivity, the intersession of reverse agonists (agouti-related peptides (AGRPs)), and interactions with accessory proteins (MRAPs).

scholarly journals Mammalian pigmentation is regulated by a distinct cAMP-dependent mechanism that controls melanosome pH

2018 ◽  
Vol 11 (555) ◽  
pp. eaau7987 ◽  
Author(s):  
Dalee Zhou ◽  
Koji Ota ◽  
Charlee Nardin ◽  
Michelle Feldman ◽  
Adam Widman ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Skin Color ◽  
Skin Pigmentation ◽  
Melanin Production ◽  
Melanocortin 1 Receptor ◽  
New Class ◽  
Camp Pathway ◽  
Human Melanocytes ◽  
Rate Limiting

The production of melanin increases skin pigmentation and reduces the risk of skin cancer. Melanin production depends on the pH of melanosomes, which are more acidic in lighter-skinned than in darker-skinned people. We showed that inhibition of soluble adenylyl cyclase (sAC) controlled pigmentation by increasing the pH of melanosomes both in cells and in vivo. Distinct from the canonical melanocortin 1 receptor (MC1R)–dependent cAMP pathway that controls pigmentation by altering gene expression, we found that inhibition of sAC increased pigmentation by increasing the activity of tyrosinase, the rate-limiting enzyme in melanin synthesis, which is more active at basic pH. We demonstrated that the effect of sAC activity on pH and melanin production in human melanocytes depended on the skin color of the donor. Last, we identified sAC inhibitors as a new class of drugs that increase melanosome pH and pigmentation in vivo, suggesting that pharmacologic inhibition of this pathway may affect skin cancer risk or pigmentation conditions.

Complementary roles of mouse lipocalins in chemical communication and immunity

2014 ◽  
Vol 42 (4) ◽  
pp. 893-898 ◽  
Author(s):  
Romana Stopková ◽  
Barbora Dudková ◽  
Petra Hájková ◽  
Pavel Stopka
Keyword(s):  
Oral Cavity ◽  
G Protein ◽  
Primary Site ◽  
G Protein Coupled Receptors ◽  
Main Route ◽  
Evolutionary Forces ◽  
Biochemical Pathways ◽  
G Protein Coupled ◽  
The Brain ◽  
Exogenous Substances

A primary site of infection in mammals is the nostrils, representing the gate to the brain through olfactory and vomeronasal epithelia, eyes as a direct route to the brain via the optical nerve, and oral cavity representing the main route to the digestive tract. Similarly, pheromones, odorants and tastants enter animal bodies the same way. Therefore similar evolutionary forces might have shaped the evolution of systems for recognition of pathogens and chemical signals. This might have resulted in sharing various proteins among systems of recognition and filtering to decrease potential costs of evolving and utilizing unique biochemical pathways. This has been documented previously in, for example, multipurpose and widely distributed GPCRs (G-protein-coupled receptors). The aim of the present review is to explore potential functional overlaps or complementary functions of lipocalins in the system of perception of exogenous substances to reconstruct the evolutionary forces that might have shaped their synergistic functions.

scholarly journals Modulation of the Serotonergic Receptosome in the Treatment of Anxiety and Depression: A Narrative Review of the Experimental Evidence

2021 ◽  
Vol 14 (2) ◽  
pp. 148
Author(s):  
Gustavo R. Villas-Boas ◽  
Stefânia N. Lavorato ◽  
Marina M. Paes ◽  
Pablinny M. G. de Carvalho ◽  
Vanessa C. Rescia ◽  
...  
Keyword(s):  
Experimental Evidence ◽  
Rational Design ◽  
Brain Regions ◽  
G Protein Coupled Receptors ◽  
New Drugs ◽  
Anxiety And Depression ◽  
Pharmacological Mechanism ◽  
Art Research ◽  
G Protein Coupled ◽  
The Brain

Serotonin (5-HT) receptors are found throughout central and peripheral nervous systems, mainly in brain regions involved in the neurobiology of anxiety and depression. 5-HT receptors are currently promising targets for discovering new drugs for treating disorders ranging from migraine to neuropsychiatric upsets, such as anxiety and depression. It is well described in the current literature that the brain expresses seven types of 5-HT receptors comprising eighteen distinct subtypes. In this article, we comprehensively reviewed 5-HT1-7 receptors. Of the eighteen 5-HT receptors known today, thirteen are G protein-coupled receptors (GPCRs) and represent targets for approximately 40% of drugs used in humans. Signaling pathways related to these receptors play a crucial role in neurodevelopment and can be modulated to develop effective therapies to treat anxiety and depression. This review presents the experimental evidence of the modulation of the “serotonergic receptosome” in the treatment of anxiety and depression, as well as demonstrating state-of-the-art research related to phytochemicals and these disorders. In addition, detailed aspects of the pharmacological mechanism of action of all currently known 5-HT receptor families were reviewed. From this review, it will be possible to direct the rational design of drugs towards new therapies that involve signaling via 5-HT receptors.

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