scholarly journals Function and Evolution of Nuclear Receptors in Environmental-Dependent Postembryonic Development

2021 ◽  
Vol 9 ◽  
Author(s):  
Jan Taubenheim ◽  
Constantin Kortmann ◽  
Sebastian Fraune
Keyword(s):  
Nuclear Receptors ◽  
Sexual Maturation ◽  
Steroid Receptors ◽  
Current Knowledge ◽  
Postembryonic Development ◽  
Model Organisms ◽  
Signaling Mechanism ◽  
Signaling Systems ◽  
Decision Points ◽  
Complex Signaling

Nuclear receptors (NRs) fulfill key roles in the coordination of postembryonal developmental transitions in animal species. They control the metamorphosis and sexual maturation in virtually all animals and by that the two main environmental-dependent developmental decision points. Sexual maturation and metamorphosis are controlled by steroid receptors and thyroid receptors, respectively in vertebrates, while both processes are orchestrated by the ecdysone receptor (EcR) in insects. The regulation of these processes depends on environmental factors like nutrition, temperature, or photoperiods and by that NRs form evolutionary conserved mediators of phenotypic plasticity. While the mechanism of action for metamorphosis and sexual maturation are well studied in model organisms, the evolution of these systems is not entirely understood and requires further investigation. We here review the current knowledge of NR involvement in metamorphosis and sexual maturation across the animal tree of life with special attention to environmental integration and evolution of the signaling mechanism. Furthermore, we compare commonalities and differences of the different signaling systems. Finally, we identify key gaps in our knowledge of NR evolution, which, if sufficiently investigated, would lead to an importantly improved understanding of the evolution of complex signaling systems, the evolution of life history decision points, and, ultimately, speciation events in the metazoan kingdom.

The glycomes of Caenorhabditis elegans and other model organisms

2002 ◽  
Vol 69 ◽  
pp. 117-134 ◽  
Author(s):  
Stuart M. Haslam ◽  
David Gems ◽  
Howard R. Morris ◽  
Anne Dell
Keyword(s):  
Caenorhabditis Elegans ◽  
Current Knowledge ◽  
Structural Data ◽  
Model Organisms ◽  
Entire Genome ◽  
C Elegans ◽  
The Face ◽  
Area Of Concern ◽  
Nematode Worm

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.

scholarly journals Research on Plants for the Understanding of Diseases of Nuclear and Mitochondrial Origin

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Claudia P. Spampinato ◽  
Diego F. Gomez-Casati
Keyword(s):  
Current Knowledge ◽  
Model System ◽  
Human Diseases ◽  
Model Organisms ◽  
Human Cell Lines ◽  
Molecular Defects ◽  
Human Genes ◽  
Clinical Disorders ◽  
Mitochondrial Origin ◽  
Experimental Findings

Different model organisms, such asEscherichia coli,Saccharomyces cerevisiae,Caenorhabditis elegans,Drosophila melanogaster, mouse, cultured human cell lines, among others, were used to study the mechanisms of several human diseases. Since human genes and proteins have been structurally and functionally conserved in plant organisms, the use of plants, especiallyArabidopsis thaliana, as a model system to relate molecular defects to clinical disorders has recently increased. Here, we briefly review our current knowledge of human diseases of nuclear and mitochondrial origin and summarize the experimental findings of plant homologs implicated in each process.

scholarly journals Hanks-Type Serine/Threonine Protein Kinases and Phosphatases in Bacteria: Roles in Signaling and Adaptation to Various Environments

2018 ◽  
Vol 19 (10) ◽  
pp. 2872 ◽  
Author(s):  
Monika Janczarek ◽  
José-María Vinardell ◽  
Paulina Lipa ◽  
Magdalena Karaś
Keyword(s):  
Dna Binding ◽  
Essential Role ◽  
Current Knowledge ◽  
Response Regulator ◽  
Protein Targets ◽  
Regulatory Pathways ◽  
Translational Machinery ◽  
Signaling Systems ◽  
Cellular Processes ◽  
Division Cell

Reversible phosphorylation is a key mechanism that regulates many cellular processes in prokaryotes and eukaryotes. In prokaryotes, signal transduction includes two-component signaling systems, which involve a membrane sensor histidine kinase and a cognate DNA-binding response regulator. Several recent studies indicate that alternative regulatory pathways controlled by Hanks-type serine/threonine kinases (STKs) and serine/threonine phosphatases (STPs) also play an essential role in regulation of many different processes in bacteria, such as growth and cell division, cell wall biosynthesis, sporulation, biofilm formation, stress response, metabolic and developmental processes, as well as interactions (either pathogenic or symbiotic) with higher host organisms. Since these enzymes are not DNA-binding proteins, they exert the regulatory role via post-translational modifications of their protein targets. In this review, we summarize the current knowledge of STKs and STPs, and discuss how these enzymes mediate gene expression in prokaryotes. Many studies indicate that regulatory systems based on Hanks-type STKs and STPs play an essential role in the regulation of various cellular processes, by reversibly phosphorylating many protein targets, among them several regulatory proteins of other signaling cascades. These data show high complexity of bacterial regulatory network, in which the crosstalk between STK/STP signaling enzymes, components of TCSs, and the translational machinery occurs. In this regulation, the STK/STP systems have been proved to play important roles.

scholarly journals ATP-dependent release of glucocorticoid receptors from the nuclear matrix.

1996 ◽  
Vol 16 (5) ◽  
pp. 1989-2001 ◽  
Author(s):  
Y Tang ◽  
D B DeFranco
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Matrix ◽  
Nuclear Export ◽  
Glucocorticoid Receptors ◽  
De Novo ◽  
Steroid Receptors ◽  
Simian Virus 40 ◽  
Atp Depletion ◽  
Nuclear Proteins ◽  
The Matrix

Glucocorticoid receptors (GRs) have the capacity to shuttle between the nuclear and cytoplasmic compartments, sharing that trait with other steroid receptors and unrelated nuclear proteins of diverse function. Although nuclear import of steroid receptors, like that of nearly all other karyophilic proteins examined to date, requires ATP, there appear to be different energetic requirements for export of proteins, including steroid receptors, from nuclei. In an attempt to reveal which steps, if any, in the nuclear export pathway utilized by steroid receptors require ATP, we have used indirect immunofluorescence to visualize GRs within cells subjected to a reversible ATP depletion. Under conditions which lead to >95% depletion of cellular ATP levels within 90 min, GRs remain localized within nuclei and do not efflux into the cytoplasm. Under analogous conditions of ATP depletion, transfected progesterone receptors are also retained within nuclei. Importantly, GRs which accumulate within nuclei of ATP-depleted cells are distinguished from nuclear receptors in metabolically active cells by their resistance to in situ extraction with a hypotonic, detergent-containing buffer. GRs in ATP-depleted cells are not permanently trapped in this nuclear compartment, as nuclear receptors rapidly regain their capacity to be extracted upon restoration of cellular ATP, even in the absence of de novo protein synthesis. More extensive extraction of cells with high salt and detergent, coupled with DNase I digestion, established that a significant fraction of GRs in ATP-depleted cells are associated with an RNA-containing nuclear matrix. Quantitative Western blot (immunoblot) analysis confirmed the dramatic increase in GR binding to the nuclear matrix of ATP-depleted cells, while confocal microscopy revealed that GRs are bound to the matrix throughout all planes of the nucleus. ATP depletion does not lead to wholesale collapse of nuclear proteins onto the matrix, as the interaction of a subpopulation of simian virus 40 large tumor antigen with the nuclear matrix is not quantitatively altered in ATP-depleted Cos-1 cells. Nuclear GRs which are not bound to the nuclear matrix of metabolically active cells (i.e., a DNA-binding domain deletion mutant and a beta-galactosidase chimera possessing the GR nuclear localization signal sequence) are not recruited to the matrix upon depletion of cellular ATP. Thus, it appears that ATP depletion does not expose the GR to nuclear matrix interactions which are not normally encountered in cells but merely alters the dynamics of such interactions. The dynamic association of steroid receptors with the nuclear matrix may provide a mechanism which is utilized by these regulable transcription factors to facilitate their efficient scanning of the genome.

scholarly journals WOMEN IN CANCER THEMATIC REVIEW: New roles for nuclear receptors in prostate cancer

2016 ◽  
Vol 23 (11) ◽  
pp. T85-T108 ◽  
Author(s):  
Damien A Leach ◽  
Sue M Powell ◽  
Charlotte L Bevan
Keyword(s):  
Prostate Cancer ◽  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Current Knowledge ◽  
Transcriptional Responses ◽  
Number Variation ◽  
Genomic Studies ◽  
Life Threatening ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

Prostate cancer has, for decades, been treated by inhibiting androgen signalling. This is effective in the majority of patients, but inevitably resistance develops and patients progress to life-threatening metastatic disease – hence the quest for new effective therapies for ‘castrate-resistant’ prostate cancer (CRPC). Studies into what pathways can drive tumour recurrence under these conditions has identified several other nuclear receptor signalling pathways as potential drivers or modulators of CRPC.The nuclear receptors constitute a large (48 members) superfamily of transcription factors sharing a common modular functional structure. Many of them are activated by the binding of small lipophilic molecules, making them potentially druggable. Even those for which no ligand exists or has yet been identified may be tractable to activity modulation by small molecules. Moreover, genomic studies have shown that in models of CRPC, other nuclear receptors can potentially drive similar transcriptional responses to the androgen receptor, while analysis of expression and sequencing databases shows disproportionately high mutation and copy number variation rates among the superfamily. Hence, the nuclear receptor superfamily is of intense interest in the drive to understand how prostate cancer recurs and how we may best treat such recurrent disease. This review aims to provide a snapshot of the current knowledge of the roles of different nuclear receptors in prostate cancer – a rapidly evolving field of research.

scholarly journals Local Secretory Trafficking Pathways in Neurons and the Role of Dendritic Golgi Outposts in Different Cell Models

2020 ◽  
Vol 13 ◽  
Author(s):  
Jingqi Wang ◽  
Lou Fourriere ◽  
Paul A. Gleeson
Keyword(s):  
Cell Body ◽  
Membrane Trafficking ◽  
Current Knowledge ◽  
Neurological Diseases ◽  
Model Organisms ◽  
Neuronal Structure ◽  
Anterograde Transport ◽  
Transport Pathways ◽  
Human Neurons

A fundamental characteristic of neurons is the relationship between the architecture of the polarized neuron and synaptic transmission between neurons. Intracellular membrane trafficking is paramount to establish and maintain neuronal structure; perturbation in trafficking results in defects in neurodevelopment and neurological disorders. Given the physical distance from the cell body to the distal sites of the axon and dendrites, transport of newly synthesized membrane proteins from the central cell body to their functional destination at remote, distal sites represents a conundrum. With the identification of secretory organelles in dendrites, including endoplasmic reticulum (ER) and Golgi outposts (GOs), recent studies have proposed local protein synthesis and trafficking distinct from the conventional anterograde transport pathways of the cell body. A variety of different model organisms, including Drosophila, zebrafish, and rodents, have been used to probe the organization and function of the local neuronal secretory network. Here, we review the evidence for local secretory trafficking pathways in dendrites in a variety of cell-based neuronal systems and discuss both the similarities and differences in the organization and role of the local secretory organelles, especially the GOs. In addition, we identify the gaps in the current knowledge and the potential advances using human induced pluripotent stem cells (iPSCs) in defining local membrane protein trafficking in human neurons and in understanding the molecular basis of neurological diseases.

Look Closely, the Beautiful May Be Small: Precursor-Derived Peptides in Plants

2019 ◽  
Vol 70 (1) ◽  
pp. 153-186 ◽  
Author(s):  
Vilde Olsson ◽  
Lisa Joos ◽  
Shanshuo Zhu ◽  
Kris Gevaert ◽  
Melinka A. Butenko ◽  
...  
Keyword(s):  
Cell Communication ◽  
Peptide Ligands ◽  
Biologically Active ◽  
Peptide Ligand ◽  
Long Distance ◽  
Signaling Systems ◽  
Experimental Approaches ◽  
Biologically Active Peptide ◽  
Subsequent Activation ◽  
Complex Signaling

During the past decade, a flurry of research focusing on the role of peptides as short- and long-distance signaling molecules in plant cell communication has been undertaken. Here, we focus on peptides derived from nonfunctional precursors, and we address several key questions regarding peptide signaling. We provide an overview of the regulatory steps involved in producing a biologically active peptide ligand that can bind its corresponding receptor(s) and discuss how this binding and subsequent activation lead to specific cellular outputs. We discuss different experimental approaches that can be used to match peptide ligands with their receptors. Lastly, we explore how peptides evolved from basic signaling units regulating essential processes in plants to more complex signaling systems as new adaptive traits developed and how nonplant organisms exploit this signaling machinery by producing peptide mimics.

scholarly journals In control of biology: of mice, men and Foxes

2006 ◽  
Vol 397 (2) ◽  
pp. 233-246 ◽  
Author(s):  
Patrick J. E. C. Wijchers ◽  
J. Peter H. Burbach ◽  
Marten P. Smidt
Keyword(s):  
Transcription Factors ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Model Organisms ◽  
Functional Protein ◽  
Comprehensive Overview ◽  
Developmental Defects ◽  
Forkhead Transcription Factors ◽  
Human Pathology ◽  
Forkhead Gene

Forkhead proteins comprise a highly conserved family of transcription factors, named after the original forkhead gene in Drosophila. To date, over 100 forkhead genes have been identified in a large variety of species, all sharing the evolutionary conserved ‘forkhead’ DNA-binding domain, and the cloning and characterization of forkhead genes have continued in recent years. Forkhead transcription factors regulate the expression of countless genes downstream of important signalling pathways in most, if not all, tissues and cell types. Recent work has provided novel insights into the mechanisms that contribute to their functional diversity, including functional protein domains and interactions of forkheads with other transcription factors. Studies using loss- and gain-of-function models have elucidated the role of forkhead factors in developmental biology and cellular functions such as metabolism, cell division and cell survival. The importance of forkhead transcription factors is underlined by the developmental defects observed in mutant model organisms, and multiple human disorders and cancers which can be attributed to mutations within members of the forkhead gene family. This review provides a comprehensive overview of current knowledge on forkhead transcription factors, from structural organization and regulatory mechanisms to cellular and developmental functions in mice and humans. Finally, we will discuss how novel insights gained from involvement of ‘Foxes’ in the mechanisms underlying human pathology may create new opportunities for treatment strategies.

scholarly journals Managing the Oocyte Meiotic Arrest—Lessons from Frogs and Jellyfish

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1150 ◽  
Author(s):  
Catherine Jessus ◽  
Catriona Munro ◽  
Evelyn Houliston
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Polar Body ◽  
Model Organisms ◽  
Oocyte Growth ◽  
M Phase ◽  
History Of ◽  
Enormous Variation ◽  
Polar Body Formation ◽  
Reliable Mechanism

During oocyte development, meiosis arrests in prophase of the first division for a remarkably prolonged period firstly during oocyte growth, and then when awaiting the appropriate hormonal signals for egg release. This prophase arrest is finally unlocked when locally produced maturation initiation hormones (MIHs) trigger entry into M-phase. Here, we assess the current knowledge of the successive cellular and molecular mechanisms responsible for keeping meiotic progression on hold. We focus on two model organisms, the amphibian Xenopus laevis, and the hydrozoan jellyfish Clytia hemisphaerica. Conserved mechanisms govern the initial meiotic programme of the oocyte prior to oocyte growth and also, much later, the onset of mitotic divisions, via activation of two key kinase systems: Cdk1-Cyclin B/Gwl (MPF) for M-phase activation and Mos-MAPkinase to orchestrate polar body formation and cytostatic (CSF) arrest. In contrast, maintenance of the prophase state of the fully-grown oocyte is assured by highly specific mechanisms, reflecting enormous variation between species in MIHs, MIH receptors and their immediate downstream signalling response. Convergence of multiple signalling pathway components to promote MPF activation in some oocytes, including Xenopus, is likely a heritage of the complex evolutionary history of spawning regulation, but also helps ensure a robust and reliable mechanism for gamete production.

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