scholarly journals Drosophila Corazonin Neurons as a Hub for Regulating Growth, Stress Responses, Ethanol-Related Behaviors, Copulation Persistence and Sexually Dimorphic Reward Pathways

2021 ◽  
Vol 9 (3) ◽  
pp. 26
Author(s):  
Ziam Khan ◽  
Maya Tondravi ◽  
Ryan Oliver ◽  
Fernando J. Vonhoff
Keyword(s):  
Stress Responses ◽  
Molecular Mechanisms ◽  
Growth Stress ◽  
Sexually Dimorphic ◽  
Behavioral Decision ◽  
Neuronal Mechanisms ◽  
Internal States ◽  
Interval Timer ◽  
Neuropeptide F ◽  
Reward Pathways

The neuronal mechanisms by which complex behaviors are coordinated and timed often involve neuropeptidergic regulation of stress and reward pathways. Recent studies of the neuropeptide Corazonin (Crz), a homolog of the mammalian Gonadotrophin Releasing Hormone (GnRH), have suggested its crucial role in the regulation of growth, internal states and behavioral decision making. We focus this review on Crz neurons with the goal to (1) highlight the diverse roles of Crz neuron function, including mechanisms that may be independent of the Crz peptide, (2) emphasize current gaps in knowledge about Crz neuron functions, and (3) propose exciting ideas of novel research directions involving the use of Crz neurons. We describe the different developmental fates of distinct subsets of Crz neurons, including recent findings elucidating the molecular regulation of apoptosis. Crz regulates systemic growth, food intake, stress responses and homeostasis by interacting with the short Neuropeptide F (sNPF) and the steroid hormone ecdysone. Additionally, activation of Crz neurons is shown to be pleasurable by interacting with the Neuropeptide F (NPF) and regulates reward processes such as ejaculation and ethanol-related behaviors in a sexually dimorphic manner. Crz neurons are proposed to be a motivational switch regulating copulation duration using a CaMKII-dependent mechanism described as the first neuronal interval timer lasting longer than a few seconds. Lastly, we propose ideas to use Crz neuron-induced ejaculation to study the effects of fictive mating and sex addiction in flies, as well as to elucidate dimorphic molecular mechanisms underlying reward behaviors and feeding disorders.

scholarly journals Interplay between brassinosteroids and TORC signaling in Arabidopsis revealed by integrated multi-dimensional analysis

2021 ◽  
Author(s):  
Christian Montes ◽  
Ching-Yi Liao ◽  
Trevor M Nolan ◽  
Gaoyuan Song ◽  
Natalie M Clark ◽  
...  
Keyword(s):  
Plant Growth ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Growth Stress ◽  
Signaling Network ◽  
Kinase Signaling ◽  
Loss Of Function ◽  
Novel Proteins ◽  
Genome Wide ◽  
Autophagy Activity

AbstractBrassinosteroids (BR) and Target of Rapamycin Complex (TORC) are two major processes coordinating plant growth and stress responses. BRs function through a signaling pathway to extensively regulate gene expression and TORC is known to regulate translation and autophagy. Recent studies revealed that these two pathways crosstalk, but a system-wide view of their interplay is still missing. Thus, we performed transcriptome, proteome, and phosphoproteome profiling of Arabidopsis mutants with altered levels of either BIN2 or RAPTOR1B, two key players in BR and TORC signaling, respectively. We found that perturbation of BIN2 or RAPTOR1B levels affects a common set of gene-products involved in growth and stress responses. Additionally, we performed Multiplexed Assay for Kinase Specificity (MAKS), which provided a system-wide view of direct BIN2 substrates. Furthermore, phosphoproteomic data was used to reconstruct a kinase-signaling network and to identify novel proteins dependent on BR and/or TORC signaling pathways. Loss of function mutants of many of these proteins led to an altered BR response and/or modulated autophagy activity. Altogether, these results provide genome-wide evidence for crosstalk between BR and TORC signaling and established a kinase signaling network that defines the molecular mechanisms of BR and TORC interactions in the regulation of plant growth/stress balance.

scholarly journals Loss of mGluR5 in D1 Receptor-Expressing Neurons Improves Stress Coping

2021 ◽  
Vol 22 (15) ◽  
pp. 7826
Author(s):  
Luca Zangrandi ◽  
Claudia Schmuckermair ◽  
Hussein Ghareh ◽  
Federico Castaldi ◽  
Regine Heilbronn ◽  
...  
Keyword(s):  
Stress Responses ◽  
Metabotropic Glutamate Receptor ◽  
Forced Swim Test ◽  
Functional Integration ◽  
D1 Receptor ◽  
Conditional Knockout ◽  
Stress Coping ◽  
Metabotropic Glutamate ◽  
Internal States

The metabotropic glutamate receptor type 5 (mGluR5) has been proposed to play a crucial role in the selection and regulation of cognitive, affective, and emotional behaviors. However, the mechanisms by which these receptors mediate these effects remain largely unexplored. Here, we studied the role of mGluR5 located in D1 receptor-expressing (D1) neurons in the manifestation of different behavioral expressions. Mice with conditional knockout (cKO) of mGluR5 in D1 neurons (mGluR5D1 cKO) and littermate controls displayed similar phenotypical profiles in relation to memory expression, anxiety, and social behaviors. However, mGluR5D1 cKO mice presented different coping mechanisms in response to acute escapable or inescapable stress. mGluR5D1 cKO mice adopted an enhanced active stress coping strategy upon exposure to escapable stress in the two-way active avoidance (TWA) task and a greater passive strategy upon exposure to inescapable stress in the forced swim test (FST). In summary, this work provides evidence for a functional integration of the dopaminergic and glutamatergic system to mediate control over internal states upon stress exposure and directly implicates D1 neurons and mGluR5 as crucial mediators of behavioral stress responses.

scholarly journals LONP1 and ClpP cooperatively regulate mitochondrial proteostasis for cancer cell survival

Oncogenesis ◽  
2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Yu Geon Lee ◽  
Hui Won Kim ◽  
Yeji Nam ◽  
Kyeong Jin Shin ◽  
Yu Jin Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Growth ◽  
Cell Survival ◽  
Cancer Cell ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Tca Cycle ◽  
Mitochondrial Matrix ◽  
Mitochondrial Functions ◽  
Cancer Cell Survival

AbstractMitochondrial proteases are key components in mitochondrial stress responses that maintain proteostasis and mitochondrial integrity in harsh environmental conditions, which leads to the acquisition of aggressive phenotypes, including chemoresistance and metastasis. However, the molecular mechanisms and exact role of mitochondrial proteases in cancer remain largely unexplored. Here, we identified functional crosstalk between LONP1 and ClpP, which are two mitochondrial matrix proteases that cooperate to attenuate proteotoxic stress and protect mitochondrial functions for cancer cell survival. LONP1 and ClpP genes closely localized on chromosome 19 and were co-expressed at high levels in most human cancers. Depletion of both genes synergistically attenuated cancer cell growth and induced cell death due to impaired mitochondrial functions and increased oxidative stress. Using mitochondrial matrix proteomic analysis with an engineered peroxidase (APEX)-mediated proximity biotinylation method, we identified the specific target substrates of these proteases, which were crucial components of mitochondrial functions, including oxidative phosphorylation, the TCA cycle, and amino acid and lipid metabolism. Furthermore, we found that LONP1 and ClpP shared many substrates, including serine hydroxymethyltransferase 2 (SHMT2). Inhibition of both LONP1 and ClpP additively increased the amount of unfolded SHMT2 protein and enhanced sensitivity to SHMT2 inhibitor, resulting in significantly reduced cell growth and increased cell death under metabolic stress. Additionally, prostate cancer patients with higher LONP1 and ClpP expression exhibited poorer survival. These results suggest that interventions targeting the mitochondrial proteostasis network via LONP1 and ClpP could be potential therapeutic strategies for cancer.

Insights into the molecular basis of host behaviour manipulation by Toxoplasma gondii infection

2017 ◽  
Vol 1 (6) ◽  
pp. 563-572 ◽  
Author(s):  
Pierre-Mehdi Hammoudi ◽  
Dominique Soldati-Favre
Keyword(s):  
Toxoplasma Gondii ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Brain Regions ◽  
Intermediate Hosts ◽  
Toxoplasma Gondii Infection ◽  
Host Parasite ◽  
Host Behaviour ◽  
The Brain ◽  
Brain Homeostasis

Typically illustrating the ‘manipulation hypothesis’, Toxoplasma gondii is widely known to trigger sustainable behavioural changes during chronic infection of intermediate hosts to enhance transmission to its feline definitive hosts, ensuring survival and dissemination. During the chronic stage of infection in rodents, a variety of neurological dysfunctions have been unravelled and correlated with the loss of cat fear, among other phenotypic impacts. However, the underlying neurological alteration(s) driving these behavioural modifications is only partially understood, which makes it difficult to draw more than a correlation between T. gondii infection and changes in brain homeostasis. Moreover, it is barely known which among the brain regions governing fear and stress responses are preferentially affected during T. gondii infection. Studies aiming at an in-depth dissection of underlying molecular mechanisms occurring at the host and parasite levels will be discussed in this review. Addressing this reminiscent topic in the light of recent technical progress and new discoveries regarding fear response, olfaction and neuromodulator mechanisms could contribute to a better understanding of this complex host–parasite interaction.

scholarly journals Human Sex Matters: Y-linked lysine demethylase 5D drives accelerated male osteogenic differentiation

2021 ◽  
Author(s):  
Madlen Merten ◽  
Johannes F.W. Greiner ◽  
Tarek Niemann ◽  
Meike Grosse Venhaus ◽  
Daniel Kronenberg ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Molecular Mechanisms ◽  
Female Rats ◽  
Sexually Dimorphic ◽  
Loss Of Function ◽  
Calvarial Bone ◽  
Sexual Dimorphisms ◽  
Increased Risk ◽  
Elevated Expression ◽  
Lysine Demethylase

Female sex is increasingly associated to a loss of bone mass during aging and an increased risk for fractures developing nonunion. Hormonal factors and cell-intrinsic mechanisms are suggested to drive these sexual dimorphisms, although underlying molecular mechanisms are still a matter of debate. Here, we observed a decreased capacity of calvarial bone recovery in female rats and a profound sexually dimorphic osteogenic differentiation human adult neural crest-derived stem cells (NCSCs). Next to an elevated expression of pro-osteogenic regulators, global trancriptomics revealed Lysine Demethylase 5D (KDM5D) to be highly upregulated in differentiating male NCSCs. Loss of function by siRNA or pharmacological inhibition of KDM5D significantly reduced the osteogenic differentiation capacity of male NCSCs. In summary, we demonstrate craniofacial osteogenic differentiation to be sexually dimorphic with the expression of KDM5D as a prerequisite for accelerated male osteogenic differentiation, emphasizing the analysis of sex-specific differences as a crucial parameter for treating bone defects.

scholarly journals Genome-wide promoter analysis, homology modeling and protein interaction network of Dehydration Responsive Element Binding (DREB) gene family in Solanum tuberosum

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261215
Author(s):  
Qurat-ul ain-Ali ◽  
Nida Mushtaq ◽  
Rabia Amir ◽  
Alvina Gul ◽  
Muhammad Tahir ◽  
...  
Keyword(s):  
Abiotic Stress ◽  
Gene Family ◽  
Stress Responses ◽  
Promoter Analysis ◽  
Molecular Mechanisms ◽  
Regulatory Elements ◽  
Start Codon ◽  
Gene Promoters ◽  
Responsive Element ◽  
Dreb Gene

Dehydration Responsive Element Binding (DREB) regulates the expression of numerous stress-responsive genes, and hence plays a pivotal role in abiotic stress responses and tolerance in plants. The study aimed to develop a complete overview of the cis-acting regulatory elements (CAREs) present in S. tuberosum DREB gene promoters. A total of one hundred and four (104) cis-regulatory elements (CREs) were identified from 2.5kbp upstream of the start codon (ATG). The in-silico promoter analysis revealed variable sets of cis-elements and functional diversity with the predominance of light-responsive (30%), development-related (20%), abiotic stress-responsive (14%), and hormone-responsive (12%) elements in StDREBs. Among them, two light-responsive elements (Box-4 and G-box) were predicted in 64 and 61 StDREB genes, respectively. Two development-related motifs (AAGAA-motif and as-1) were abundant in StDREB gene promoters. Most of the DREB genes contained one or more Myeloblastosis (MYB) and Myelocytometosis (MYC) elements associated with abiotic stress responses. Hormone-responsive element i.e. ABRE was found in 59 out of 66 StDREB genes, which implied their role in dehydration and salinity stress. Moreover, six proteins were chosen corresponding to A1-A6 StDREB subgroups for secondary structure analysis and three-dimensional protein modeling followed by model validation through PROCHECK server by Ramachandran Plot. The predicted models demonstrated >90% of the residues in the favorable region, which further ensured their reliability. The present study also anticipated pocket binding sites and disordered regions (DRs) to gain insights into the structural flexibility and functional annotation of StDREB proteins. The protein association network determined the interaction of six selected StDREB proteins with potato proteins encoded by other gene families such as MYB and NAC, suggesting their similar functional roles in biological and molecular pathways. Overall, our results provide fundamental information for future functional analysis to understand the precise molecular mechanisms of the DREB gene family in S. tuberosum.

scholarly journals Altered metal distribution in the sr45-1 Arabidopsis mutant causes developmental defects

2021 ◽  
Author(s):  
Steven Fanara ◽  
Marie Schloesser ◽  
Marc Hanikenne ◽  
Patrick Motte
Keyword(s):  
Stress Responses ◽  
Molecular Mechanisms ◽  
Phenylpropanoid Pathway ◽  
Histochemical Staining ◽  
Metal Distribution ◽  
Iron Starvation ◽  
Developmental Defects ◽  
Developmental Abnormalities ◽  
Arabidopsis Mutant ◽  
Root Tissues

The plant SR (serine/arginine-rich) splicing factor SR45 plays important roles in several biological processes, such as splicing, DNA methylation, innate immunity, glucose regulation and ABA signaling. A homozygous Arabidopsis sr45-1 null mutant is viable, but exhibits diverse phenotypic alterations, including delayed root development, late flowering, shorter siliques with fewer seeds, narrower leaves and petals, and unusual numbers of floral organs. Here, we report that the sr45-1 mutant presents an unexpected constitutive iron deficiency phenotype characterized by altered metal distribution in the plant. RNA-Sequencing highlighted severe perturbations in metal homeostasis, phenylpropanoid pathway, oxidative stress responses, and reproductive development. Ionomic quantification and histochemical staining revealed strong iron accumulation in the sr45-1 root tissues accompanied by an iron starvation in aerial parts. We showed that some sr45-1 developmental abnormalities can be complemented by exogenous iron supply. Our findings provide new insight into the molecular mechanisms governing the phenotypes of the sr45-1 mutant.

scholarly journals Functions of PPR Proteins in Plant Growth and Development

2021 ◽  
Vol 22 (20) ◽  
pp. 11274
Author(s):  
Xiulan Li ◽  
Mengdi Sun ◽  
Shijuan Liu ◽  
Qian Teng ◽  
Shihui Li ◽  
...  
Keyword(s):  
Plant Growth ◽  
Stress Responses ◽  
Rna Processing ◽  
Growth And Development ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Plant Mitochondria ◽  
Research Progress ◽  
Plant Growth And Development ◽  
Ppr Proteins

Pentatricopeptide repeat (PPR) proteins form a large protein family in land plants, with hundreds of different members in angiosperms. In the last decade, a number of studies have shown that PPR proteins are sequence-specific RNA-binding proteins involved in multiple aspects of plant organellar RNA processing, and perform numerous functions in plants throughout their life cycle. Recently, computational and structural studies have provided new insights into the working mechanisms of PPR proteins in RNA recognition and cytidine deamination. In this review, we summarized the research progress on the functions of PPR proteins in plant growth and development, with a particular focus on their effects on cytoplasmic male sterility, stress responses, and seed development. We also documented the molecular mechanisms of PPR proteins in mediating RNA processing in plant mitochondria and chloroplasts.

scholarly journals Overexpression of SgGH3.1 from Fine-Stem Stylo (Stylosanthes guianensis var. intermedia) Enhances Chilling and Cold Tolerance in Arabidopsis thaliana

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1367
Author(s):  
Ming Jiang ◽  
Long-Long Ma ◽  
Huai-An Huang ◽  
Shan-Wen Ke ◽  
Chun-Sheng Gui ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Cold Stress ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Transcriptome Profiling ◽  
Pasture Legumes ◽  
Cold Tolerant ◽  
Whole Transcriptome ◽  
Altered Sensitivity ◽  
Exogenous Iaa

Stylosanthes (stylo) species are commercially significant tropical and subtropical forage and pasture legumes that are vulnerable to chilling and frost. However, little is known about the molecular mechanisms behind stylos’ responses to low temperature stress. Gretchen-Hagen 3 (GH3) proteins have been extensively investigated in many plant species for their roles in auxin homeostasis and abiotic stress responses, but none have been reported in stylos. SgGH3.1, a cold-responsive gene identified in a whole transcriptome profiling study of fine-stem stylo (S. guianensis var. intermedia) was further investigated for its involvement in cold stress tolerance. SgGH3.1 shared a high percentage of identity with 14 leguminous GH3 proteins, ranging from 79% to 93%. Phylogenetic analysis classified SgGH3.1 into Group Ⅱ of GH3 family, which have been proven to involve with auxins conjugation. Expression profiling revealed that SgGH3.1 responded rapidly to cold stress in stylo leaves. Overexpression of SgGH3.1 in Arabidopsis thaliana altered sensitivity to exogenous IAA, up-regulated transcription of AtCBF1-3 genes, activated physiological responses against cold stress, and enhanced chilling and cold tolerances. This is the first report of a GH3 gene in stylos, which not only validated its function in IAA homeostasis and cold responses, but also gave insight into breeding of cold-tolerant stylos.

scholarly journals Inhibition of 11β-HSD1 Ameliorates Cognition and Molecular Detrimental Changes after Chronic Mild Stress in SAMP8 Mice

2021 ◽  
Vol 14 (10) ◽  
pp. 1040
Author(s):  
Dolors Puigoriol-Illamola ◽  
Júlia Companys-Alemany ◽  
Kris McGuire ◽  
Natalie Z. M. Homer ◽  
Rosana Leiva ◽  
...  
Keyword(s):  
Stress Responses ◽  
Healthy Aging ◽  
Molecular Mechanisms ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Cognitive Improvement ◽  
Age Related ◽  
Mtorc1 Signaling ◽  
Cognitive Disturbances ◽  
Samp8 Mice

Impaired glucocorticoid (GC) signaling is a significant factor in aging, stress, and neurodegenerative diseases such as Alzheimer’s disease. Therefore, the study of GC-mediated stress responses to chronic moderately stressful situations, which occur in daily life, is of huge interest for the design of pharmacological strategies toward the prevention of neurodegeneration. To address this issue, SAMP8 mice were exposed to the chronic mild stress (CMS) paradigm for 4 weeks and treated with RL-118, an 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor. The inhibition of this enzyme is linked with a reduction in GC levels and cognitive improvement, while CMS exposure has been associated with reduced cognitive performance. The aim of this project was to assess whether RL-118 treatment could reverse the deleterious effects of CMS on cognition and behavioral abilities and to evaluate the molecular mechanisms that compromise healthy aging in SAMP8 mice. First, we confirmed the target engagement between RL-118 and 11β-HSD1. Additionally, we showed that DNA methylation, hydroxymethylation, and histone phosphorylation were decreased by CMS induction, and increased by RL-118 treatment. In addition, CMS exposure caused the accumulation of reactive oxygen species (ROS)-induced damage and increased pro-oxidant enzymes—as well as pro-inflammatory mediators—through the NF-κB pathway and astrogliosis markers, such as GFAP. Of note, these modifications were reversed by 11β-HSD1 inhibition. Remarkably, although CMS altered mTORC1 signaling, autophagy was increased in the SAMP8 RL-118-treated mice. We also showed an increase in amyloidogenic processes and a decrease in synaptic plasticity and neuronal remodeling markers in mice under CMS, which were consequently modified by RL-118 treatment. In conclusion, 11β-HSD1 inhibition through RL-118 ameliorated the detrimental effects induced by CMS, including epigenetic and cognitive disturbances, indicating that GC-excess attenuation shows potential as a therapeutic strategy for age-related cognitive decline and AD.

Sign in / Sign up

Export Citation Format

Share Document