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G Protein-Coupled Receptors and Their Kinases in Cell Biology and Disease (Closed)

A topical collection in International Journal of Molecular Sciences (ISSN 1422-0067). This collection belongs to the section "Molecular Biology".

Viewed by 33087

Editor

Dr. Alessandro Cannavo

E-Mail Website
Collection Editor
Department of Translational Medical Sciences, University of Naples Federico II, 80138 Naples, Italy
Interests: cardiovascular disease; G protein coupled receptor; neurodegenerative disorders; periodontitis; pharmacology
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

Over the past three decades, since Nobel prize winners Robert Lefkowitz and Brian Kobilka characterized the structure of G protein-coupled receptors (GPCRs), a great deal of clinical and pharmacological evidence has advanced our knowledge of how these receptors and their signaling pathways influence almost every aspect of mammals’ physiology. GPCRs can transduce cellular signals from neurohormones, sensory stimuli, and ions, and their activity is directly modulated by GPCR kinases (GRKs), phosphorylation, and subsequent desensitization. Nevertheless, an alteration in GRKs’ expression, with subsequent GPCR dysfunction, may induce—or at least influence—the development and progression of different systemic disorders. Thus, several drugs which are able to directly inhibit or enhance GPCR signaling have been developed and are currently used in clinical practice.

This Topical Collection calls for both original articles and reviews providing readers of IJMS with a comprehensive elucidation of the GPCR and GRK functions in cell biology that is necessary for developing novel research approaches as well as therapeutic strategies.

Dr. Alessandro Cannavo
Collection Editor

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Keywords

  • Cell biology
  • Cardiovascular disease
  • G protein-coupled receptor
  • GRK ischemia
  • Neurodegeneration
  • Inflammation
  • Metabolism
  • Pharmacology

Published Papers (12 papers)

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2023

Jump to: 2022

25 pages, 11717 KiB  
Article
Dynamics of the Second Extracellular Loop Control Transducer Coupling of Peptide-Activated GPCRs
by Marcel M. Wygas, Jeannette M. Laugwitz, Peter Schmidt, Matthias Elgeti and Anette Kaiser
Int. J. Mol. Sci. 2023, 24(15), 12197; https://doi.org/10.3390/ijms241512197 - 30 Jul 2023
Viewed by 2582
Abstract
Many peptide-activated rhodopsin-like GPCRs share a β-hairpin folding motif in the extracellular loop 2 (ECL2), which interacts with the peptide ligand while at the same time being connected to transmembrane helix 3 (TM3) via a highly conserved disulfide bond. Currently, it remains unknown [...] Read more.
Many peptide-activated rhodopsin-like GPCRs share a β-hairpin folding motif in the extracellular loop 2 (ECL2), which interacts with the peptide ligand while at the same time being connected to transmembrane helix 3 (TM3) via a highly conserved disulfide bond. Currently, it remains unknown whether the coupling of the specifically shaped ECL2 to TM3 influences the activation of peptide-activated GPCRs. We investigated this possibility in a selection of peptide GPCRs with known structures. Most of the receptors with cysteine to alanine mutations folded like the respective wild-type and resided in the cell membrane, challenging pure folding stabilization by the disulfide bridge. G-protein signaling of the disulfide mutants was retained to a greater extent in secretin-like GPCRs than in rhodopsin-like GPCRs, while recruitment of arrestin was completely abolished in both groups, which may be linked to alterations in ligand residence time. We found a correlation between receptor activity of the neuropeptide Y2 receptor and alterations in ECL2 dynamics using engineered disulfide bridges or site-directed spin labeling and EPR spectroscopy. These data highlight the functional importance of the TM3-ECL2 link for the activation of specific signaling pathways in peptide-activated GPCRs, which might have implications for future drug discovery. Full article
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2022

Jump to: 2023

2 pages, 1626 KiB  
Correction
Correction: Chen et al. The Chemerin/CMKLR1 Axis Is Involved in the Recruitment of Microglia to Aβ Deposition through p38 MAPK Pathway. Int. J. Mol. Sci. 2022, 23, 9041
by Yanqing Chen, Zhen Liu, Ping Gong, Haibo Zhang, Yijun Chen, Songquan Yao, Wei Li, Yan Zhang and Yang Yu
Int. J. Mol. Sci. 2023, 24(1), 506; https://doi.org/10.3390/ijms24010506 - 28 Dec 2022
Cited by 33 | Viewed by 1222
Abstract
In the original publication [...] Full article
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16 pages, 1697 KiB  
Review
The Role of G Protein-Coupled Receptor Kinase 6 Regulation in Inflammation and Pain
by Maike Stegen and Ulrich H. Frey
Int. J. Mol. Sci. 2022, 23(24), 15880; https://doi.org/10.3390/ijms232415880 - 14 Dec 2022
Cited by 6 | Viewed by 2231
Abstract
The G protein-coupled receptor kinase 6 is associated with inflammation and pathological pain. Impairment of GRK6 expression was described in chronic inflammatory diseases such as rheumatoid arthritis and this was shown to be accompanied by an imbalance of downstream signaling pathways. Here, we [...] Read more.
The G protein-coupled receptor kinase 6 is associated with inflammation and pathological pain. Impairment of GRK6 expression was described in chronic inflammatory diseases such as rheumatoid arthritis and this was shown to be accompanied by an imbalance of downstream signaling pathways. Here, we discuss novel aspects of GRK6 interaction and its impact upon hyperalgesia and inflammatory processes. In this review, we compile important findings concerning GRK6 regulation for a better pathophysiological understanding of the intracellular interaction in the context of inflammation and show clinical implications—for example, the identification of possible therapy goals in the treatment of chronic inflammatory hyperalgesia. Full article
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20 pages, 2861 KiB  
Review
The Role of Reversible Phosphorylation of Drosophila Rhodopsin
by Thomas K. Smylla, Krystina Wagner and Armin Huber
Int. J. Mol. Sci. 2022, 23(23), 14674; https://doi.org/10.3390/ijms232314674 - 24 Nov 2022
Viewed by 2358
Abstract
Vertebrate and fly rhodopsins are prototypical GPCRs that have served for a long time as model systems for understanding GPCR signaling. Although all rhodopsins seem to become phosphorylated at their C-terminal region following activation by light, the role of this phosphorylation is not [...] Read more.
Vertebrate and fly rhodopsins are prototypical GPCRs that have served for a long time as model systems for understanding GPCR signaling. Although all rhodopsins seem to become phosphorylated at their C-terminal region following activation by light, the role of this phosphorylation is not uniform. Two major functions of rhodopsin phosphorylation have been described: (1) inactivation of the activated rhodopsin either directly or by facilitating binding of arrestins in order to shut down the visual signaling cascade and thus eventually enabling a high-temporal resolution of the visual system. (2) Facilitating endocytosis of activated receptors via arrestin binding that in turn recruits clathrin to the membrane for clathrin-mediated endocytosis. In vertebrate rhodopsins the shutdown of the signaling cascade may be the main function of rhodopsin phosphorylation, as phosphorylation alone already quenches transducin activation and, in addition, strongly enhances arrestin binding. In the Drosophila visual system rhodopsin phosphorylation is not needed for receptor inactivation. Its role here may rather lie in the recruitment of arrestin 1 and subsequent endocytosis of the activated receptor. In this review, we summarize investigations of fly rhodopsin phosphorylation spanning four decades and contextualize them with regard to the most recent insights from vertebrate phosphorylation barcode theory. Full article
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13 pages, 1365 KiB  
Review
G Protein-Coupled Receptors Regulated by Membrane Potential
by Dekel David, Ziv Bentulila, Merav Tauber and Yair Ben-Chaim
Int. J. Mol. Sci. 2022, 23(22), 13988; https://doi.org/10.3390/ijms232213988 - 12 Nov 2022
Cited by 8 | Viewed by 2151
Abstract
G protein-coupled receptors (GPCRs) are involved in a vast majority of signal transduction processes. Although they span the cell membrane, they have not been considered to be regulated by the membrane potential. Numerous studies over the last two decades have demonstrated that several [...] Read more.
G protein-coupled receptors (GPCRs) are involved in a vast majority of signal transduction processes. Although they span the cell membrane, they have not been considered to be regulated by the membrane potential. Numerous studies over the last two decades have demonstrated that several GPCRs, including muscarinic, adrenergic, dopaminergic, and glutamatergic receptors, are voltage regulated. Following these observations, an effort was made to elucidate the molecular basis for this regulatory effect. In this review, we will describe the advances in understanding the voltage dependence of GPCRs, the suggested molecular mechanisms that underlie this phenomenon, and the possible physiological roles that it may play. Full article
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24 pages, 5728 KiB  
Article
Design, Synthesis and Biological Evaluation of Novel 1,3,5-Triazines: Effect of Aromatic Ring Decoration on Affinity to 5-HT7 Receptor
by Damian Kułaga, Anna Karolina Drabczyk, Grzegorz Satała, Gniewomir Latacz, Anna Boguszewska-Czubara, Damian Plażuk and Jolanta Jaśkowska
Int. J. Mol. Sci. 2022, 23(21), 13308; https://doi.org/10.3390/ijms232113308 - 1 Nov 2022
Cited by 5 | Viewed by 2452
Abstract
Considering the key functions of the 5-HT7 receptor, especially in psychiatry, and the fact that effective and selective 5-HT7 receptor ligands are yet to be available, in this work, we designed and synthesized novel 1,3,5-triazine derivatives particularly based on the evaluation [...] Read more.
Considering the key functions of the 5-HT7 receptor, especially in psychiatry, and the fact that effective and selective 5-HT7 receptor ligands are yet to be available, in this work, we designed and synthesized novel 1,3,5-triazine derivatives particularly based on the evaluation of the effect of substituents at aromatic rings on biological activity. The tested compounds showed high affinity to the 5-HT7 receptor, particularly ligands N2-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N4-phenethyl-1,3,5-triazine-2,4,6-triamine 2 (Ki = 8 nM) and N2-(2-(1H-indol-3-yl)ethyl)-N4-(2-((4-fluorophenyl)amino)ethyl)-1,3,5-triazine-2,4,6-triamine 12 (Ki = 18 nM) which showed moderate metabolic stability, and affinity to the CYP3A4 isoenzyme. As for the hepatotoxicity evaluation, the tested compounds showed moderate cytotoxicity only at concentrations above 50 µM. Compound 12 exhibited less cardiotoxic effect than 2 on Danio rerio in vivo model. Full article
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11 pages, 1139 KiB  
Review
Functions of the Zinc-Sensing Receptor GPR39 in Regulating Intestinal Health in Animals
by Pengpeng Xia, Li Yan, Xingduo Ji, Yunping Wu, Siqi Lian and Guoqiang Zhu
Int. J. Mol. Sci. 2022, 23(20), 12133; https://doi.org/10.3390/ijms232012133 - 12 Oct 2022
Cited by 4 | Viewed by 2477
Abstract
G protein-coupled receptor 39 (GPR39) is a zinc-sensing receptor (ZnR) that can sense changes in extracellular Zn2+, mediate Zn2+ signal transmission, and participate in the regulation of numerous physiological activities in living organisms. For example, GPR39 activates the extracellular signal-regulated [...] Read more.
G protein-coupled receptor 39 (GPR39) is a zinc-sensing receptor (ZnR) that can sense changes in extracellular Zn2+, mediate Zn2+ signal transmission, and participate in the regulation of numerous physiological activities in living organisms. For example, GPR39 activates the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) and phosphatidylinositol3-kinase/protein kinase B (PI3K/AKT) signaling pathways upon Zn2+ stimulation, enhances the proliferation and differentiation of colonic cells, and regulates ion transport, as well as exerting other functions. In recent years, with the increased attention to animal gut health issues and the intensive research on GPR39, GPR39 has become a potential target for regulating animal intestinal health. On the one hand, GPR39 is involved in regulating ion transport in the animal intestine, mediating the Cl− efflux by activating the K+/Cl− synergistic protein transporter, and relieving diarrhea symptoms. On the other hand, GPR39 can maintain the homeostasis of the animal intestine, promoting pH restoration in colonic cells, regulating gastric acid secretion, and facilitating nutrient absorption. In addition, GPR39 can affect the expression of tight junction proteins in intestinal epithelial cells, improving the barrier function of the animal intestinal mucosa, and maintaining the integrity of the intestine. This review summarizes the structure and signaling transduction processes involving GPR39 and the effect of GPR39 on the regulation of intestinal health in animals, with the aim of further highlighting the role of GPR39 in regulating animal intestinal health and providing new directions and ideas for studying the prevention and treatment of animal intestinal diseases. Full article
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19 pages, 3738 KiB  
Article
The Chemerin/CMKLR1 Axis Is Involved in the Recruitment of Microglia to Aβ Deposition through p38 MAPK Pathway
by Yanqing Chen, Zhen Liu, Ping Gong, Haibo Zhang, Yijun Chen, Songquan Yao, Wei Li, Yan Zhang and Yang Yu
Int. J. Mol. Sci. 2022, 23(16), 9041; https://doi.org/10.3390/ijms23169041 - 12 Aug 2022
Cited by 10 | Viewed by 2835 | Correction
Abstract
The accumulation of microglia around senile plaques is one of the pathological features of Alzheimer’s disease (AD). Chemerin is an adipokine with immune-modulating properties. Our previous study showed that chemokine-like receptor 1 (CMKLR1), the receptor for chemerin, is also a functional receptor of [...] Read more.
The accumulation of microglia around senile plaques is one of the pathological features of Alzheimer’s disease (AD). Chemerin is an adipokine with immune-modulating properties. Our previous study showed that chemokine-like receptor 1 (CMKLR1), the receptor for chemerin, is also a functional receptor of Aβ. However, it remains unclear whether and how the chemerin/CMKLR1 axis affects the migration of microglia. The impact of CMKLR1 on microglial activation and recruitment toward Aβ deposits was examined in APP/PS1 mice mated with CMKLR1 knockout (CMKLR1−/−) mice. CMKLR1 deficiency reduced the number of microglia around Aβ deposits in aged APP/PS1-CMKLR1−/− mice compared with APP/PS1 mice. Chemerin expression was significantly decreased in the hippocampus and cortex of aged APP/PS1 mice compared with WT mice. In vitro assays demonstrated that activation of the chemerin/CMKLR1 axis promoted the migration of primary cultures of microglia and murine microglial N9 cells. Mechanistic studies found that chemerin/CMKLR1 induced polarization and protrusion formation of microglia by promoting the remodeling of actin filaments and microtubules, and Golgi apparatus reorientation. The inhibition of p38 MAPK attenuated the promotion of the chemerin/CMKLR1 axis on microglial migration and polarization. In addition, chemerin inhibited Aβ-induced microglial clustering. The inhibition of p38 MAPK alleviated the suppressive effect of chemerin on Aβ-induced microglial aggregation. Our data indicate that the chemerin/CMKLR1 axis is involved in the migration and recruitment of microglia to senile plaques via the p38 MAPK pathway. Modulation of the chemerin/CMKLR1 axis is a potential new strategy for AD therapy. Full article
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30 pages, 3856 KiB  
Article
Bromocriptine-QR Therapy Reduces Sympathetic Tone and Ameliorates a Pro-Oxidative/Pro-Inflammatory Phenotype in Peripheral Blood Mononuclear Cells and Plasma of Type 2 Diabetes Subjects
by Anthony H. Cincotta, Eugenio Cersosimo, Mariam Alatrach, Michael Ezrokhi, Christina Agyin, John Adams, Robert Chilton, Curtis Triplitt, Bindu Chamarthi, Nicholas Cominos and Ralph A. DeFronzo
Int. J. Mol. Sci. 2022, 23(16), 8851; https://doi.org/10.3390/ijms23168851 - 9 Aug 2022
Cited by 8 | Viewed by 4075
Abstract
Bromocriptine-QR is a sympatholytic dopamine D2 agonist for the treatment of type 2 diabetes that has demonstrated rapid (within 1 year) substantial reductions in adverse cardiovascular events in this population by as yet incompletely delineated mechanisms. However, a chronic state of elevated sympathetic [...] Read more.
Bromocriptine-QR is a sympatholytic dopamine D2 agonist for the treatment of type 2 diabetes that has demonstrated rapid (within 1 year) substantial reductions in adverse cardiovascular events in this population by as yet incompletely delineated mechanisms. However, a chronic state of elevated sympathetic nervous system activity and central hypodopaminergic function has been demonstrated to potentiate an immune system pro-oxidative/pro-inflammatory condition and this immune phenotype is known to contribute significantly to the advancement of cardiovascular disease (CVD). Therefore, the possibility exists that bromocriptine-QR therapy may reduce adverse cardiovascular events in type 2 diabetes subjects via attenuation of this underlying chronic pro-oxidative/pro-inflammatory state. The present study was undertaken to assess the impact of bromocriptine-QR on a wide range of immune pro-oxidative/pro-inflammatory biochemical pathways and genes known to be operative in the genesis and progression of CVD. Inflammatory peripheral blood mononuclear cell biology is both a significant contributor to cardiovascular disease and also a marker of the body’s systemic pro-inflammatory status. Therefore, this study investigated the effects of 4-month circadian-timed (within 2 h of waking in the morning) bromocriptine-QR therapy (3.2 mg/day) in type 2 diabetes subjects whose glycemia was not optimally controlled on the glucagon-like peptide 1 receptor agonist on (i) gene expression status (via qPCR) of a wide array of mononuclear cell pro-oxidative/pro-inflammatory genes known to participate in the genesis and progression of CVD (OXR1, NRF2, NQO1, SOD1, SOD2, CAT, GSR, GPX1, GPX4, GCH1, HMOX1, BiP, EIF2α, ATF4, PERK, XBP1, ATF6, CHOP, GSK3β, NFkB, TXNIP, PIN1, BECN1, TLR2, TLR4, TLR10, MAPK8, NLRP3, CCR2, GCR, L-selectin, VCAM1, ICAM1) and (ii) humoral measures of sympathetic tone (norepinephrine and normetanephrine), whole-body oxidative stress (nitrotyrosine, TBARS), and pro-inflammatory factors (IL-1β, IL-6, IL-18, MCP-1, prolactin, C-reactive protein [CRP]). Relative to pre-treatment status, 4 months of bromocriptine-QR therapy resulted in significant reductions of mRNA levels in PBMC endoplasmic reticulum stress-unfolded protein response effectors [GRP78/BiP (34%), EIF2α (32%), ATF4 (29%), XBP1 (25%), PIN1 (14%), BECN1 (23%)], oxidative stress response proteins [OXR1 (31%), NRF2 (32%), NQO1 (39%), SOD1 (52%), CAT (26%), GPX1 (33%), GPX4 (31%), GCH1 (30%), HMOX1 (40%)], mRNA levels of TLR pro-inflammatory pathway proteins [TLR2 (46%), TLR4 (20%), GSK3β (19%), NFkB (33%), TXNIP (18%), NLRP3 (32%), CCR2 (24%), GCR (28%)], mRNA levels of pro-inflammatory cellular receptor proteins CCR2 and GCR by 24% and 28%, and adhesion molecule proteins L-selectin (35%) and VCAM1 (24%). Relative to baseline, bromocriptine-QR therapy also significantly reduced plasma levels of norepinephrine and normetanephrine by 33% and 22%, respectively, plasma pro-oxidative markers nitrotyrosine and TBARS by 13% and 10%, respectively, and pro-inflammatory factors IL-18, MCP1, IL-1β, prolactin, and CRP by 21%,13%, 12%, 42%, and 45%, respectively. These findings suggest a unique role for circadian-timed bromocriptine-QR sympatholytic dopamine agonist therapy in reducing systemic low-grade sterile inflammation to thereby reduce cardiovascular disease risk. Full article
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39 pages, 6640 KiB  
Article
Biological Role of the Intercellular Transfer of Glycosylphosphatidylinositol-Anchored Proteins: Stimulation of Lipid and Glycogen Synthesis
by Günter A. Müller and Timo D. Müller
Int. J. Mol. Sci. 2022, 23(13), 7418; https://doi.org/10.3390/ijms23137418 - 4 Jul 2022
Cited by 5 | Viewed by 2434
Abstract
Glycosylphosphatidylinositol-anchored proteins (GPI-APs), which are anchored at the outer leaflet of plasma membranes (PM) only by a carboxy-terminal GPI glycolipid, are known to fulfill multiple enzymic and receptor functions at the cell surface. Previous studies revealed that full-length GPI-APs with the complete GPI [...] Read more.
Glycosylphosphatidylinositol-anchored proteins (GPI-APs), which are anchored at the outer leaflet of plasma membranes (PM) only by a carboxy-terminal GPI glycolipid, are known to fulfill multiple enzymic and receptor functions at the cell surface. Previous studies revealed that full-length GPI-APs with the complete GPI anchor attached can be released from and inserted into PMs in vitro. Moreover, full-length GPI-APs were recovered from serum, dependent on the age and metabolic state of rats and humans. Here, the possibility of intercellular control of metabolism by the intercellular transfer of GPI-APs was studied. Mutant K562 erythroleukemia (EL) cells, mannosamine-treated human adipocytes and methyl-ß-cyclodextrin-treated rat adipocytes as acceptor cells for GPI-APs, based on their impaired PM expression of GPI-APs, were incubated with full-length GPI-APs, prepared from rat adipocytes and embedded in micelle-like complexes, or with EL cells and human adipocytes with normal expression of GPI-APs as donor cells in transwell co-cultures. Increases in the amounts of full-length GPI-APs at the PM of acceptor cells as a measure of their transfer was assayed by chip-based sensing. Both experimental setups supported both the transfer and upregulation of glycogen (EL cells) and lipid (adipocytes) synthesis. These were all diminished by serum, serum GPI-specific phospholipase D, albumin, active bacterial PI-specific phospholipase C or depletion of total GPI-APs from the culture medium. Serum inhibition of both transfer and glycogen/lipid synthesis was counteracted by synthetic phosphoinositolglycans (PIGs), which closely resemble the structure of the GPI glycan core and caused dissociation of GPI-APs from serum proteins. Finally, large, heavily lipid-loaded donor and small, slightly lipid-loaded acceptor adipocytes were most effective in stimulating transfer and lipid synthesis. In conclusion, full-length GPI-APs can be transferred between adipocytes or between blood cells as well as between these cell types. Transfer and the resulting stimulation of lipid and glycogen synthesis, respectively, are downregulated by serum proteins and upregulated by PIGs. These findings argue for the (patho)physiological relevance of the intercellular transfer of GPI-APs in general and its role in the paracrine vs. endocrine (dys)regulation of metabolism, in particular. Moreover, they raise the possibility of the use of full-length GPI-APs as therapeutics for metabolic diseases. Full article
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18 pages, 9790 KiB  
Review
Serotonin Receptors as Therapeutic Targets for Autism Spectrum Disorder Treatment
by Ansoo Lee, Hyunah Choo and Byungsun Jeon
Int. J. Mol. Sci. 2022, 23(12), 6515; https://doi.org/10.3390/ijms23126515 - 10 Jun 2022
Cited by 20 | Viewed by 4674
Abstract
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by repetitive and stereotyped behaviors as well as difficulties with social interaction and communication. According to reports for prevalence rates of ASD, approximately 1~2% of children worldwide have been diagnosed with ASD. [...] Read more.
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by repetitive and stereotyped behaviors as well as difficulties with social interaction and communication. According to reports for prevalence rates of ASD, approximately 1~2% of children worldwide have been diagnosed with ASD. Although there are a couple of FDA (Food and Drug Administration)—approved drugs for ASD treatment such as aripiprazole and risperidone, they are efficient for alleviating aggression, hyperactivity, and self-injury but not the core symptoms. Serotonin (5-hydroxytryptamine, 5-HT) as a neurotransmitter plays a crucial role in the early neurodevelopmental stage. In particular, 5-HT has been known to regulate a variety of neurobiological processes including neurite outgrowth, dendritic spine morphology, shaping neuronal circuits, synaptic transmission, and synaptic plasticity. Given the roles of serotonergic systems, the 5-HT receptors (5-HTRs) become emerging as potential therapeutic targets in the ASD. In this review, we will focus on the recent development of small molecule modulators of 5-HTRs as therapeutic targets for the ASD treatment. Full article
20 pages, 3237 KiB  
Article
The First Homologous Expression System for the β-Lytic Protease of Lysobacter capsici VKM B-2533T, a Promising Antimicrobial Agent
by Irina Kudryakova, Alexey Afoshin, Elena Leontyevskaya and Natalia Leontyevskaya (Vasilyeva)
Int. J. Mol. Sci. 2022, 23(10), 5722; https://doi.org/10.3390/ijms23105722 - 20 May 2022
Cited by 3 | Viewed by 1769
Abstract
A successful homologous expression system based on Lysobacter capsici VKM B-2533T and the plasmid pBBR1-MCS5 was first developed for a promising bacteriolytic enzyme of this bacterium, β-lytic protease (Blp). In the expression strains, blp gene expression under the regulation of the GroEL(A) [...] Read more.
A successful homologous expression system based on Lysobacter capsici VKM B-2533T and the plasmid pBBR1-MCS5 was first developed for a promising bacteriolytic enzyme of this bacterium, β-lytic protease (Blp). In the expression strains, blp gene expression under the regulation of the GroEL(A) and T5 promoters increased by 247- and 667-fold, respectively, as compared with the wild-type strain. After the cultivation of the expression strains L. capsici PGroEL(A)-blp and L. capsici PT5-blp, the Blp yield increased by 6.7- and 8.5-fold, respectively, with respect to the wild-type strain. The cultivation of the expression strain L. capsici PT5-blp was successfully scaled up. Under fermentation conditions the yield of the enzyme increased by 1.6-fold. The developed homologous system was used to express the gene of the bacteriolytic serine protease (Serp) of L. capsici VKM B-2533T. The expression of the serp gene in L. capsici PT5-serp increased by 585-fold. The developed homologous system for the gene expression of bacteriolytic Lysobacter enzymes is potentially biotechnologically valuable, and is promising for creating highly efficient expression strains. Full article
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