Gene expression and phosphoprotein profile of certain key neuronal signaling proteins following soman intoxication

Chapter 4 covers postreceptor intracellular messenger cascades through which neurotransmitters and neurotrophic factors, and their receptors, produce their diverse physiological effects. A major advance over the past generation of research has been an appreciation of the complex webs of intracellular signaling pathways that control every aspect of a neuron’s functioning, from neurotransmitter signaling to cell shape and motility to gene expression. While only a small number of medications used in psychiatry today have as their initial target intracellular signaling proteins, it is likely that drug development efforts will look increasingly to such proteins for the discovery of novel medications with fundamentally new mechanisms of action.

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Optogenetic pharmacology for control of native neuronal signaling proteins

Nature Neuroscience ◽

10.1038/nn.3424 ◽

2013 ◽

Vol 16 (7) ◽

pp. 816-823 ◽

Cited By ~ 143

Author(s):

Richard H Kramer ◽

Alexandre Mourot ◽

Hillel Adesnik

Keyword(s):

Signaling Proteins ◽

Neuronal Signaling

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Mitochondria-Related Nuclear Gene Expression in the Nucleus Accumbens and Blood Mitochondrial Copy Number After Developmental Fentanyl Exposure in Adolescent Male and Female C57BL/6 Mice

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.737389 ◽

2021 ◽

Vol 12 ◽

Author(s):

Cali A. Calarco ◽

Megan E. Fox ◽

Saskia Van Terheyden ◽

Makeda D. Turner ◽

Jason B. Alipio ◽

...

Keyword(s):

Gene Expression ◽

Nucleus Accumbens ◽

Mitochondrial Function ◽

Copy Number ◽

Drug Exposure ◽

Related Gene ◽

Developmental Exposure ◽

Neuronal Signaling ◽

Mitochondrial Copy Number ◽

The Brain

The potency of the synthetic opioid fentanyl and its increased clinical availability has led to the rapid escalation of use in the general population, increased recreational exposure, and subsequently opioid-related overdoses. The wide-spread use of fentanyl has, consequently, increased the incidence of in utero exposure to the drug, but the long-term effects of this type of developmental exposure are not yet understood. Opioid use has also been linked to reduced mitochondrial copy number in blood in clinical populations, but the link between this peripheral biomarker and genetic or functional changes in reward-related brain circuitry is still unclear. Additionally, mitochondrial-related gene expression in reward-related brain regions has not been examined in the context of fentanyl exposure, despite the growing literature demonstrating drugs of abuse impact mitochondrial function, which subsequently impacts neuronal signaling. The current study uses exposure to fentanyl via dam access to fentanyl drinking water during gestation and lactation as a model for developmental drug exposure. This perinatal drug-exposure is sufficient to impact mitochondrial copy number in circulating blood leukocytes, as well as mitochondrial-related gene expression in the nucleus accumbens (NAc), a reward-related brain structure, in a sex-dependent manner in adolescent offspring. Specific NAc gene expression is correlated with both blood mitochondrial copy number and with anxiety related behaviors dependent on developmental exposure to fentanyl and sex. These data indicate that developmental fentanyl exposure impacts mitochondrial function in both the brain and body in ways that can impact neuronal signaling and may prime the brain for altered reward-related behavior in adolescence and later into adulthood.

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Understanding the early cold response mechanism in IR64 indica rice variety through comparative transcriptome analysis

10.21203/rs.2.18315/v2 ◽

2020 ◽

Author(s):

Pratiti Dasgupta ◽

Abhishek Das ◽

Sambit Datta New ◽

Ishani Banerjee New ◽

Sucheta Tripathy ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Low Temperature ◽

Cold Stress ◽

Cold Shock ◽

Indica Rice ◽

Cellular Reprogramming ◽

Early Gene ◽

Signaling Proteins ◽

Cold Response

Abstract Background Cellular reprogramming in response to environmental stress involves alteration of gene expression, changes in the protein and metabolite profile for ensuring better stress management in plants. Similar to other plant species originating in tropical and sub-tropical areas, indica rice is highly sensitive to low temperature that adversely affects its growth and grain productivity. Substantial work has been done to understand cold induced changes in gene expression in rice plants. However, adequate information is not available for early gene expression, especially in indica variety. Therefore, a transcriptome profile was generated for cold shock treated seedlings of IR64 variety to identify early responsive genes. Results The functional annotation of early DEGs shows enrichment of genes involved in altered membrane rigidity and electrolytic leakage, the onset of calcium signaling, ROS generation and activation of stress responsive transcription factors in IR64. Gene regulatory network suggests that cold shock induces Ca 2+ signaling to activate DREB/CBF pathway and other groups of transcription factors such as MYB, NAC and ZFP; for activating various cold-responsive genes. The analysis also indicates that cold induced signaling proteins like RLKs, RLCKs, CDPKs and MAPKK and ROS signaling proteins. Further, several LEA, dehydrins and Low temperature-induced-genes were upregulated under early cold shock condition, indicating the onset of water-deficit conditions. Expression profiling in different high yielding cultivars shows high expression of cold-responsive genes in Heera and CB1 indica varieties, These varieties show low levels of cold induced ROS production, electrolytic leakage and high germination rate post-cold stress, compared to IR36 and IR64. Collectively, these results suggest that these varieties may have improved adaptability to cold stress. Conclusions The results of this study provide insights about early responsive events in Oryza sativa L.ssp. indica cv IR64 in response to cold stress. Our data shows the onset of cold response is associated with upregulation of stress responsive TFs, hydrophilic proteins and signaling molecules, whereas, the genes coding for cellular biosynthetic enzymes, cell cycle control and growth-related TFs are downregulated. This study reports that the generation of ROS is integral to the early response to trigger the ROS mediated signaling events during later stages.

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Control of bacterial anti-phage signaling by a WYL domain transcription factor

10.1101/2022.01.04.474952 ◽

2022 ◽

Author(s):

Chelsea L Blankenchip ◽

Justin V Nguyen ◽

Rebecca K Lau ◽

Qiaozhen Ye ◽

Yajie Gu ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Dna Binding ◽

Promoter Region ◽

Bound State ◽

Signaling Proteins ◽

Abortive Infection ◽

Immune Systems ◽

Dna Binding Domains ◽

Binding Domains

Bacteria use diverse immune systems to defend themselves from ubiquitous viruses termed bacteriophages (phages). Many anti-phage systems function by abortive infection to kill a phage-infected cell, raising the question of how these systems are regulated to avoid activation and cell killing outside the context of infection. Here, we identify a transcription factor associated with the widespread CBASS bacterial immune system, that we term CapW. CapW forms a homodimer and binds a palindromic DNA sequence in the CBASS promoter region. Two crystal structures of CapW reveal how the protein switches from a DNA binding-competent state to a ligand-bound state that cannot bind DNA due to misalignment of dimer-related DNA binding domains. We show that CapW strongly represses CBASS gene expression in uninfected cells, and that CapW disruption likely results in toxicity due to uncontrolled CBASS expression. Our results parallel recent findings with BrxR, a transcription factor associated with the BREX anti-phage system, and suggest that CapW and BrxR are the founding members of a family of universal anti-phage signaling proteins.

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Engineered protein switches for exogenous control of gene expression

Biochemical Society Transactions ◽

10.1042/bst20200441 ◽

2020 ◽

Vol 48 (5) ◽

pp. 2205-2212

Author(s):

Shaun Spisak ◽

Marc Ostermeier

Keyword(s):

Gene Expression ◽

Domain Swapping ◽

Signaling Proteins ◽

Genetic Circuits ◽

Control Of Gene Expression ◽

Regulate Gene Expression ◽

Substrate Specificities ◽

Large Pool ◽

Domain Insertion ◽

Exogenous Control

There is an ongoing need in the synthetic biology community for novel ways to regulate gene expression. Protein switches, which sense biological inputs and respond with functional outputs, represent one way to meet this need. Despite the fact that there is already a large pool of transcription factors and signaling proteins available, the pool of existing switches lacks the substrate specificities and activities required for certain applications. Therefore, a large number of techniques have been applied to engineer switches with novel properties. Here we discuss some of these techniques by broadly organizing them into three approaches. We show how novel switches can be created through mutagenesis, domain swapping, or domain insertion. We then briefly discuss their use as biosensors and in complex genetic circuits.

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BCL-2 inhibition with ABT-737 prolongs survival in an NRAS/BCL-2 mouse model of AML by targeting primitive LSK and progenitor cells

Blood ◽

10.1182/blood-2012-07-445635 ◽

2013 ◽

Vol 122 (16) ◽

pp. 2864-2876 ◽

Cited By ~ 31

Author(s):

Stephanie Beurlet ◽

Nader Omidvar ◽

Petra Gorombei ◽

Patricia Krief ◽

Carole Le Pogam ◽

...

Keyword(s):

Gene Expression ◽

Mouse Model ◽

Gene Expression Profiling ◽

Progenitor Cells ◽

Expression Profiling ◽

Ras Signaling ◽

Signaling Proteins ◽

Key Points ◽

Proliferation And Differentiation ◽

Domain 3

Key Points BCL-2 homology domain 3 mimetic inhibitor ABT-737 targets leukemia initiating cells and progenitors. Dephosphorylates RAS signaling proteins and regulates proliferation and differentiation genes detected by gene expression profiling.

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Nitric Oxide-Induced Murine Hematopoietic Stem Cell Fate Involves Multiple Signaling Proteins, Gene Expression, and Redox Modulation

Stem Cells ◽

10.1002/stem.1773 ◽

2014 ◽

Vol 32 (11) ◽

pp. 2949-2960 ◽

Cited By ~ 21

Author(s):

Amanda Nogueira-Pedro ◽

Carolina C. Dias ◽

Helena Regina ◽

C. Segreto ◽

Priscilla C. Addios ◽

...

Keyword(s):

Gene Expression ◽

Nitric Oxide ◽

Stem Cell ◽

Cell Fate ◽

Signaling Proteins ◽

Redox Modulation ◽

Hematopoietic Stem ◽

Stem Cell Fate ◽

Murine Hematopoietic Stem Cell ◽

Multiple Signaling

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Dorsomedial hypothalamic NPY affects cholecystokinin-induced satiety via modulation of brain stem catecholamine neuronal signaling

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00184.2015 ◽

2016 ◽

Vol 311 (5) ◽

pp. R930-R939 ◽

Cited By ~ 7

Author(s):

Claire B. de La Serre ◽

Yonwook J. Kim ◽

Timothy H. Moran ◽

Sheng Bi

Keyword(s):

Gene Expression ◽

Food Intake ◽

Neural Systems ◽

Adeno Associated Virus ◽

Dorsomedial Hypothalamus ◽

Neuronal Signaling ◽

Catecholaminergic Neurons ◽

Nucleus Of Solitary Tract ◽

Close Proximity ◽

Feeding Effects

Increased neuropeptide Y (NPY) gene expression in the dorsomedial hypothalamus (DMH) has been shown to cause hyperphagia, but the pathway underlying this effect remains less clear. Hypothalamic neural systems play a key role in the control of food intake, in part, by modulating the effects of meal-related signals, such as cholecystokinin (CCK). An increase in DMH NPY gene expression decreases CCK-induced satiety. Since activation of catecholaminergic neurons within the nucleus of solitary tract (NTS) contributes to the feeding effects of CCK, we hypothesized that DMH NPY modulates NTS neural catecholaminergic signaling to affect food intake. We used an adeno-associated virus system to manipulate DMH NPY gene expression in rats to examine this pathway. Viral-mediated hrGFP anterograde tracing revealed that DMH NPY neurons project to the NTS; the projections were in close proximity to catecholaminergic neurons, and some contained NPY. Viral-mediated DMH NPY overexpression resulted in an increase in NPY content in the NTS, a decrease in NTS tyrosine hydroxylase (TH) expression, and reduced exogenous CCK-induced satiety. Knockdown of DMH NPY produced the opposite effects. Direct NPY administration into the fourth ventricle of intact rats limited CCK-induced satiety and overall TH phosphorylation. Taken together, these results demonstrate that DMH NPY descending signals affect CCK-induced satiety, at least in part, via modulation of NTS catecholaminergic neuronal signaling.

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