scholarly journals Serotonin GPCR-based biosensing modalities in yeast

2021 ◽  
Author(s):  
Bettina Lengger ◽  
Emma E. Hoch-Schneider ◽  
Christina Noerskov ◽  
Tadas Jakociunas ◽  
Emil D. Jensen ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Resolution ◽  
G Proteins ◽  
Reporter Gene ◽  
G Protein Coupled Receptors ◽  
Human Populations ◽  
Physiological Processes ◽  
G Protein Coupled ◽  
Health Applications

Serotonin is a key neurotransmitter involved in numerous physiological processes and serves as an important precursor for manufacturing bioactive indoleamines and alkaloids used in the treatment of human pathologies. In humans, serotonin sensing and signaling can occur by 12 G protein-coupled receptors (GPCRs) coupled to G proteins. To systematically assess serotonin GPCR signaling, we characterized reporter gene expression of a 144-sized library encoding all 12 human serotonin GPCRs in combination with 12 different Gα proteins in yeast exposed to serotonin. For the 5-HT4 receptor, we observe 25- and 64-fold changes in EC50 values and dynamic reporter gene outputs, respectively. Furthermore, we show that optimal biosensing designs enable high-resolution sensing of serotonin produced in yeast, as well as provide a platform for characterization of 19 serotonin GPCR polymorphisms found in human populations. Taken together, our study highlights serotonin biosensing modalities of relevance to both biotechnological and human health applications.

scholarly journals Histamine, Metabolic Remodelling and Angiogenesis: A Systems Level Approach

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 415
Author(s):  
Aurelio A. Moya-García ◽  
Almudena Pino-Ángeles ◽  
Francisca Sánchez-Jiménez ◽  
José Luis Urdiales ◽  
Miguel Ángel Medina
Keyword(s):  
Research Field ◽  
G Protein Coupled Receptors ◽  
Signalling Pathways ◽  
Histamine Metabolism ◽  
Current Information ◽  
Physiological Processes ◽  
Cell Growth And Differentiation ◽  
G Protein Coupled

Histamine is a highly pleiotropic biogenic amine involved in key physiological processes including neurotransmission, immune response, nutrition, and cell growth and differentiation. Its effects, sometimes contradictory, are mediated by at least four different G-protein coupled receptors, which expression and signalling pathways are tissue-specific. Histamine metabolism conforms a very complex network that connect many metabolic processes important for homeostasis, including nitrogen and energy metabolism. This review brings together and analyses the current information on the relationships of the “histamine system” with other important metabolic modules in human physiology, aiming to bridge current information gaps. In this regard, the molecular characterization of the role of histamine in the modulation of angiogenesis-mediated processes, such as cancer, makes a promising research field for future biomedical advances.

scholarly journals Signaling from G Protein-coupled Receptors to ERK5/Big MAPK 1 Involves Gαqand Gα12/13Families of Heterotrimeric G Proteins

2000 ◽  
Vol 275 (28) ◽  
pp. 21730-21736 ◽  
Author(s):  
Shigetomo Fukuhara ◽  
Maria Julia Marinissen ◽  
Mario Chiariello ◽  
J. Silvio Gutkind
Keyword(s):  
G Protein ◽  
G Proteins ◽  
G Protein Coupled Receptors ◽  
Heterotrimeric G Proteins ◽  
G Protein Coupled

Compartmentalization of GPCR signalling controls unique cellular responses

2016 ◽  
Vol 44 (2) ◽  
pp. 562-567 ◽  
Author(s):  
Andrew M. Ellisdon ◽  
Michelle L. Halls
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Attrition Rates ◽  
Physiological Processes ◽  
Simple Chain ◽  
G Protein Coupled ◽  
Major Drug ◽  
Very High

With >800 members, G protein-coupled receptors (GPCRs) are the largest class of cell-surface signalling proteins, and their activation mediates diverse physiological processes. GPCRs are ubiquitously distributed across all cell types, involved in many diseases and are major drug targets. However, GPCR drug discovery is still characterized by very high attrition rates. New avenues for GPCR drug discovery may be provided by a recent shift away from the traditional view of signal transduction as a simple chain of events initiated from the plasma membrane. It is now apparent that GPCR signalling is restricted to highly organized compartments within the cell, and that GPCRs activate distinct signalling pathways once internalized. A high-resolution understanding of how compartmentalized signalling is controlled will probably provide unique opportunities to selectively and therapeutically target GPCRs.

scholarly journals The Role of Prokineticin 2 in Oxidative Stress and in Neuropathological Processes

2021 ◽  
Vol 12 ◽  
Author(s):  
Roberta Lattanzi ◽  
Cinzia Severini ◽  
Daniela Maftei ◽  
Luciano Saso ◽  
Aldo Badiani
Keyword(s):  
Pain Perception ◽  
G Protein Coupled Receptors ◽  
Cellular Processes ◽  
Prokineticin 2 ◽  
Physiological Processes ◽  
Pathological Conditions ◽  
Double Function ◽  
The Central Nervous System ◽  
G Protein Coupled

The prokineticin (PK) family, prokineticin 1 and Bv8/prokineticin 2 (PROK2), initially discovered as regulators of gastrointestinal motility, interacts with two G protein-coupled receptors, PKR1 and PKR2, regulating important biological functions such as circadian rhythms, metabolism, angiogenesis, neurogenesis, muscle contractility, hematopoiesis, immune response, reproduction and pain perception. PROK2 and PK receptors, in particular PKR2, are widespread distributed in the central nervous system, in both neurons and glial cells. The PROK2 expression levels can be increased by a series of pathological insults, such as hypoxia, reactive oxygen species, beta amyloid and excitotoxic glutamate. This suggests that the PK system, participating in different cellular processes that cause neuronal death, can be a key mediator in neurological/neurodegenerative diseases. While many PROK2/PKRs effects in physiological processes have been documented, their role in neuropathological conditions is not fully clarified, since PROK2 can have a double function in the mechanisms underlying to neurodegeneration or neuroprotection. Here, we briefly outline the latest findings on the modulation of PROK2 and its cognate receptors following different pathological insults, providing information about their opposite neurotoxic and neuroprotective role in different pathological conditions.

scholarly journals Physiology of the orexinergic/hypocretinergic system: a revisit in 2012

2013 ◽  
Vol 304 (1) ◽  
pp. C2-C32 ◽  
Author(s):  
Jyrki P. Kukkonen
Keyword(s):  
Central Nervous System ◽  
G Proteins ◽  
Cellular Responses ◽  
G Protein Coupled Receptors ◽  
Heterotrimeric G Proteins ◽  
Neuronal Excitation ◽  
System A ◽  
The Central Nervous System ◽  
G Protein Coupled ◽  
Systemic Responses

The neuropeptides orexins and their G protein-coupled receptors, OX1and OX2, were discovered in 1998, and since then, their role has been investigated in many functions mediated by the central nervous system, including sleep and wakefulness, appetite/metabolism, stress response, reward/addiction, and analgesia. Orexins also have peripheral actions of less clear physiological significance still. Cellular responses to the orexin receptor activity are highly diverse. The receptors couple to at least three families of heterotrimeric G proteins and other proteins that ultimately regulate entities such as phospholipases and kinases, which impact on neuronal excitation, synaptic plasticity, and cell death. This article is a 10-year update of my previous review on the physiology of the orexinergic/hypocretinergic system. I seek to provide a comprehensive update of orexin physiology that spans from the molecular players in orexin receptor signaling to the systemic responses yet emphasizing the cellular physiological aspects of this system.

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