scholarly journals Advances and Perspectives of Light-gated Phosphodiesterases for Optogenetic Applications

2020 ◽  
Author(s):  
Yuehui Tian ◽  
Shang Yang ◽  
Shiqiang Gao
Keyword(s):  
Intracellular Signaling ◽  
Second Messengers ◽  
Cell Physiology ◽  
Intracellular Camp ◽  
Animal Cells ◽  
Signaling Mechanism ◽  
Surface Receptors ◽  
Cgmp Signaling ◽  
Pros And Cons ◽  
Camp And Cgmp

Second messengers, cyclic adenosine 3'-5'-monophosphate (cAMP) and cyclic guanosine 3'-5'-monophosphate (cGMP) are playing important roles in many animal cells by regulating intracellular signaling pathways and modulating cell physiology. Environmental cues like temperature, light and chemical compounds can stimulate cell surface receptors and trigger the generation of second messengers and the following regulations. Spread of cAMP and cGMP is further shaped by cyclic nucleotide phosphodiesterases (PDEs) for orchestration of intracellular microdomain signaling. However, localized intracellular cAMP and cGMP signaling requires further investigation. Optogenetic manipulation of cAMP and cGMP offers new opportunities of spatio-temporally precise study of their signaling mechanism. Light-gated nucleotide cyclases are well developed and applied for cAMP/cGMP manipulation. Recently discovered rhodopsin phosphodiesterase gene from protists established new and direct biological connection between light and PDEs. Light-regulated PDEs are under development and of demand to complete the toolkit of cAMP/cGMP manipulation. In this review, we summarize the state of the art, pros and cons of artificial and natural light-regulated PDEs and discuss potential new strategies of developing light-gated PDEs for optogenetic manipulation.

scholarly journals Advances, Perspectives and Potential Engineering Strategies of Light-Gated Phosphodiesterases for Optogenetic Applications

2020 ◽  
Vol 21 (20) ◽  
pp. 7544
Author(s):  
Yuehui Tian ◽  
Shang Yang ◽  
Shiqiang Gao
Keyword(s):  
Intracellular Signaling ◽  
Second Messengers ◽  
Cell Physiology ◽  
Intracellular Camp ◽  
Animal Cells ◽  
Signaling Mechanism ◽  
Surface Receptors ◽  
Cgmp Signaling ◽  
Pros And Cons ◽  
Camp And Cgmp

The second messengers, cyclic adenosine 3′-5′-monophosphate (cAMP) and cyclic guanosine 3′-5′-monophosphate (cGMP), play important roles in many animal cells by regulating intracellular signaling pathways and modulating cell physiology. Environmental cues like temperature, light, and chemical compounds can stimulate cell surface receptors and trigger the generation of second messengers and the following regulations. The spread of cAMP and cGMP is further shaped by cyclic nucleotide phosphodiesterases (PDEs) for orchestration of intracellular microdomain signaling. However, localized intracellular cAMP and cGMP signaling requires further investigation. Optogenetic manipulation of cAMP and cGMP offers new opportunities for spatio-temporally precise study of their signaling mechanism. Light-gated nucleotide cyclases are well developed and applied for cAMP/cGMP manipulation. Recently discovered rhodopsin phosphodiesterase genes from protists established a new and direct biological connection between light and PDEs. Light-regulated PDEs are under development, and of demand to complete the toolkit for cAMP/cGMP manipulation. In this review, we summarize the state of the art, pros and cons of artificial and natural light-regulated PDEs, and discuss potential new strategies of developing light-gated PDEs for optogenetic manipulation.

scholarly journals Ca2+ Microdomains, Calcineurin and the Regulation of Gene Transcription

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 875
Author(s):  
Gerald Thiel ◽  
Tobias Schmidt ◽  
Oliver G. Rössler
Keyword(s):  
Transcription Factors ◽  
Protein Kinase ◽  
Protein Kinases ◽  
Gene Transcription ◽  
Intracellular Signaling ◽  
Second Messengers ◽  
Major Function ◽  
Surface Receptors ◽  
Dependent Protein

Ca2+ ions function as second messengers regulating many intracellular events, including neurotransmitter release, exocytosis, muscle contraction, metabolism and gene transcription. Cells of a multicellular organism express a variety of cell-surface receptors and channels that trigger an increase of the intracellular Ca2+ concentration upon stimulation. The elevated Ca2+ concentration is not uniformly distributed within the cytoplasm but is organized in subcellular microdomains with high and low concentrations of Ca2+ at different locations in the cell. Ca2+ ions are stored and released by intracellular organelles that change the concentration and distribution of Ca2+ ions. A major function of the rise in intracellular Ca2+ is the change of the genetic expression pattern of the cell via the activation of Ca2+-responsive transcription factors. It has been proposed that Ca2+-responsive transcription factors are differently affected by a rise in cytoplasmic versus nuclear Ca2+. Moreover, it has been suggested that the mode of entry determines whether an influx of Ca2+ leads to the stimulation of gene transcription. A rise in cytoplasmic Ca2+ induces an intracellular signaling cascade, involving the activation of the Ca2+/calmodulin-dependent protein phosphatase calcineurin and various protein kinases (protein kinase C, extracellular signal-regulated protein kinase, Ca2+/calmodulin-dependent protein kinases). In this review article, we discuss the concept of gene regulation via elevated Ca2+ concentration in the cytoplasm and the nucleus, the role of Ca2+ entry and the role of enzymes as signal transducers. We give particular emphasis to the regulation of gene transcription by calcineurin, linking protein dephosphorylation with Ca2+ signaling and gene expression.

STa and cGMP stimulate CFTR translocation to the surface of villus enterocytes in rat jejunum and is regulated by protein kinase G

2005 ◽  
Vol 289 (3) ◽  
pp. C708-C716 ◽  
Author(s):  
Franca Golin-Bisello ◽  
Neil Bradbury ◽  
Nadia Ameen
Keyword(s):  
Protein Kinase ◽  
Fluid Secretion ◽  
Secretory Diarrhea ◽  
Apical Plasma Membrane ◽  
Intracellular Camp ◽  
Rat Jejunum ◽  
Fourfold Increase ◽  
Anion Secretion ◽  
Cgmp Signaling ◽  
Camp And Cgmp

The cystic fibrosis transmembrane conductance regulator (CFTR) is critical to cAMP- and cGMP-activated intestinal anion secretion and the pathogenesis of secretory diarrhea. Enterotoxins released by Vibrio cholerae (cholera toxin) and Escherichia coli (heat stable enterotoxin, or STa) activate intracellular cAMP and cGMP and signal CFTR on the apical plasma membrane of small intestinal enterocytes to elicit chloride and fluid secretion. cAMP activates PKA, whereas cGMP signals a cGMP-dependent protein kinase (cGKII) to phosphorylate CFTR in the intestine. In the jejunum, cAMP also regulates CFTR and fluid secretion by insertion of CFTR from subapical vesicles to the surface of enterocytes. It is unknown whether cGMP signaling or phosphorylation regulates the insertion of CFTR associated vesicles from the cytoplasm to the surface of enterocytes. We used STa, cell-permeant cGMP, and cAMP agonists in conjunction with PKG and PKA inhibitors, respectively, in rat jejunum to examine whether 1) cGMP and cGK II regulate the translocation of CFTR to the apical membrane and its relevance to fluid secretion, and 2) PKA regulates cAMP-dependent translocation of CFTR because this intestinal segment is a primary target for toxigenic diarrhea. STa and cGMP induced a greater than fourfold increase in surface CFTR in enterocytes in association with fluid secretion that was inhibited by PKG inhibitors. cAMP agonists induced a translocation of CFTR to the cell surface of enterocytes that was prevented by PKA inhibitors. We conclude that cAMP and cGMP-dependent phosphorylation regulates fluid secretion and CFTR trafficking to the surface of enterocytes in rat jejunum.

scholarly journals β-Arrestin 2 Is a Mediator of GnRH-(1–5) Signaling in Immortalized GnRH Neurons

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4726-4736 ◽  
Author(s):  
Darwin O. Larco ◽  
Nina N. Semsarzadeh ◽  
Madelaine Cho-Clark ◽  
Shaila K. Mani ◽  
T. John Wu
Keyword(s):  
Signaling Pathway ◽  
G Protein ◽  
Intracellular Signaling ◽  
Second Messengers ◽  
Biologically Active ◽  
Inositol Triphosphate ◽  
G Protein Coupled Receptor ◽  
Signaling Mechanism ◽  
Gnrh Neurons ◽  
G Protein Coupled

We have previously demonstrated that the cleavage product of the full-length GnRH, GnRH-(1–5), is biologically active, binds G protein-coupled receptor 173 (GPR173), and inhibits the migration of cells in the immortalized GnRH-secreting GN11 cell. In this study, we attempted to characterize the GnRH-(1–5) intracellular signaling mechanism. To determine whether the signaling pathway mediating GnRH-(1–5) regulation of migration involves a G protein-dependent mechanism, cells were treated with a generic G protein antagonist in the presence and absence of GnRH-(1–5), and a wound-healing assay was conducted to measure migration. G Protein antagonist 2 treatment abolished the GnRH-(1–5) inhibition of migration, indicating that the mechanism of GnRH-(1–5) is G protein coupled. To identify the potential Gα-subunit recruited by GnRH-(1–5) binding GPR173, we measured the second messengers cAMP and inositol triphosphate levels. GnRH-(1–5) treatment did not alter cAMP levels relative to cells treated with vehicle or forskolin, suggesting that GnRH-(1–5) does not couple to the Gαs or Gαi subunits. Similarly, inositol triphosphate levels remained unchanged with GnRH-(1–5) treatment, indicating a mechanism not mediated by the Gαq/11 subunit. Therefore, we also examined whether GnRH-(1–5) activating GPR173 deviated from the canonical G protein-coupled receptor signaling pathway by coupling to β-arrestin 1/2 to regulate migration. Our coimmunoprecipitation studies indicate that GnRH-(1–5) induces the rapid interaction between GPR173 and β-arrestin 2 in GN11 cells. Furthermore, we demonstrate that this association recruits phosphatase and tensin homolog to mediate the downstream action of GnRH-(1–5). These findings suggest that the GnRH-(1–5) mechanism deviates from the canonical G protein-coupled receptor pathway to regulate cell migration in immortalized GnRH neurons.

scholarly journals Lysosomes, Autophagy, and Hormesis in Cell Physiology, Pathology, and Age-Related Disease

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582093422 ◽  
Author(s):  
Michael N. Moore
Keyword(s):  
Intracellular Signaling ◽  
Adenosine Monophosphate ◽  
Target Of Rapamycin ◽  
Cell Physiology ◽  
Mechanistic Target Of Rapamycin ◽  
Age Related ◽  
Mechanistic Basis ◽  
The Many ◽  
Mtor Complex 1

Autophagy has been strongly linked with hormesis, however, it is only relatively recently that the mechanistic basis underlying this association has begun to emerge. Lysosomal autophagy is a group of processes that degrade proteins, protein aggregates, membranes, organelles, segregated regions of cytoplasm, and even parts of the nucleus in eukaryotic cells. These degradative processes are evolutionarily very ancient and provide a survival capability for cells that are stressed or injured. Autophagy and autophagic dysfunction have been linked with many aspects of cell physiology and pathology in disease processes; and there is now intense interest in identifying various therapeutic strategies involving its regulation. The main regulatory pathway for augmented autophagy is the mechanistic target of rapamycin (mTOR) cell signaling, although other pathways can be involved, such as 5′-adenosine monophosphate-activated protein kinase. Mechanistic target of rapamycin is a key player in the many highly interconnected intracellular signaling pathways and is responsible for the control of cell growth among other processes. Inhibition of mTOR (specifically dephosphorylation of mTOR complex 1) triggers augmented autophagy and the search is on the find inhibitors that can induce hormetic responses that may be suitable for treating many diseases, including many cancers, type 2 diabetes, and age-related neurodegenerative conditions.

scholarly journals Antimicrobial Peptides and Physical Activity: A Great Hope against COVID 19

2021 ◽  
Vol 9 (7) ◽  
pp. 1415
Author(s):  
Sonia Laneri ◽  
Mariarita Brancaccio ◽  
Cristina Mennitti ◽  
Margherita G. De Biasi ◽  
Maria Elena Pero ◽  
...  
Keyword(s):  
Physical Activity ◽  
Antimicrobial Peptides ◽  
Intracellular Signaling ◽  
Chemokine Receptors ◽  
Healthy Lifestyle ◽  
Direct Interaction ◽  
Vaccine Adjuvants ◽  
Viral Inhibition ◽  
Immune Modulators ◽  
Surface Receptors

Antimicrobial peptides (AMPs), α- and β-defensins, possess antiviral properties. These AMPs achieve viral inhibition through different mechanisms of action. For example, they can: (i) bind directly to virions; (ii) bind to and modulate host cell-surface receptors, disrupting intracellular signaling; (iii) function as chemokines to augment and alter adaptive immune responses. Given their antiviral properties and the fact that the development of an effective coronavirus disease 2019 (COVID-19) treatment is an urgent public health priority, they and their derivatives are being explored as potential therapies against COVID-19. These explorations using various strategies, range from their direct interaction with the virus to using them as vaccine adjuvants. However, AMPs do not work in isolation, specifically in their role as potent immune modulators, where they interact with toll-like receptors (TLRs) and chemokine receptors. Both of these receptors have been shown to play roles in COVID-19 pathogenesis. In addition, it is known that a healthy lifestyle accompanied by controlled physical activity can represent a natural weapon against COVID-19. In competitive athletes, an increase in serum defensins has been shown to function as self-protection from the attack of microorganisms, consequently a controlled physical activity could act as a support to any therapies in fighting COVID-19. Therefore, including information on all these players’ interactions would produce a complete picture of AMP-based therapies’ response.

scholarly journals Proliferative and Apoptotic Pathways in the Testis of Quail Coturnix coturnix during the Seasonal Reproductive Cycle

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1729
Author(s):  
Sara Falvo ◽  
Luigi Rosati ◽  
Maria Maddalena Di Fiore ◽  
Federica Di Giacomo Russo ◽  
Gabriella Chieffi Baccari ◽  
...  
Keyword(s):  
Reproductive Cycle ◽  
Second Messengers ◽  
Reproductive Period ◽  
Annual Reproductive Cycle ◽  
Coturnix Coturnix ◽  
Immunohistochemistry Analysis ◽  
17Β Estradiol ◽  
Apoptotic Pathways ◽  
Camp And Cgmp ◽  
Activation Phase

The quail Coturnix coturnix is a seasonal breeding species, with the annual reproductive cycle of its testes comprising an activation phase and a regression phase. Our previous results have proven that the testicular levels of both 17β-estradiol (E2) and androgens are higher during the reproductive period compared to the non-reproductive period, which led us to hypothesize that estrogens and androgens may act synergistically to initiate spermatogenesis. The present study was, therefore, aimed to investigate the estrogen responsive system in quail testis in relation to the reproduction seasonality, with a focus on the molecular pathways elicited in both active and regressive quail testes. Western blotting and immunohistochemistry analysis revealed that the expression of ERα, which is the predominant form of estrogen receptors in quail testis, was correlated with E2 concentration, suggesting that increased levels of E2-induced ERα could play a key role in the resumption of spermatogenesis during the reproductive period, when both PCNA and SYCP3, the mitotic and meiotic markers, respectively, were also increased. In the reproductive period we also found the activation of the ERK1/2 and Akt-1 kinase pathways and an increase in second messengers cAMP and cGMP levels. In the non-reproductive phase, when the E2/ERα levels were low, the inactivation of ERK1/2 and Akt-1 pathways favored apoptotic events due to an increase in the levels of Bax and cytochrome C, with a consequent regression of the gonad.

scholarly journals Plasma Polymerized Allylamine—The Unique Cell-Attractive Nanolayer for Dental Implant Materials

Polymers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1004 ◽  
Author(s):  
J. Barbara Nebe ◽  
Henrike Rebl ◽  
Michael Schlosser ◽  
Susanne Staehlke ◽  
Martina Gruening ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Microwave Plasma ◽  
Cell Attachment ◽  
Tetragonal Zirconia ◽  
Surrounding Tissue ◽  
Material Surface ◽  
Cell Physiology ◽  
Ceramic Surface ◽  
Plasma Chemical ◽  
Unique Cell

Biomaterials should be bioactive in stimulating the surrounding tissue to accelerate the ingrowth of permanent implants. Chemical and topographical features of the biomaterial surface affect cell physiology at the interface. A frequently asked question is whether the chemistry or the topography dominates the cell-material interaction. Recently, we demonstrated that a plasma-chemical modification using allylamine as a precursor was able to boost not only cell attachment and cell migration, but also intracellular signaling in vital cells. This microwave plasma process generated a homogenous nanolayer with randomly distributed, positively charged amino groups. In contrast, the surface of the human osteoblast is negatively charged at −15 mV due to its hyaluronan coat. As a consequence, we assumed that positive charges at the material surface—provoking electrostatic interaction forces—are attractive for the first cell encounter. This plasma-chemical nanocoating can be used for several biomaterials in orthopedic and dental implantology like titanium, titanium alloys, calcium phosphate scaffolds, and polylactide fiber meshes produced by electrospinning. In this regard, we wanted to ascertain whether plasma polymerized allylamine (PPAAm) is also suitable for increasing the attractiveness of a ceramic surface for dental implants using Yttria-stabilized tetragonal zirconia.

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