scholarly journals Neural integrity is maintained by dystrophin in C. elegans

2011 ◽  
Vol 192 (2) ◽  
pp. 349-363 ◽  
Author(s):  
Shan Zhou ◽  
Lihsia Chen
Keyword(s):  
Membrane Integrity ◽  
Muscle Membrane ◽  
Dependent Manner ◽  
Neuronal Function ◽  
C Elegans ◽  
Neural Organization ◽  
Associated Proteins ◽  
Duchenne's Muscular Dystrophy ◽  
Dystrophin Protein

The dystrophin protein complex (DPC), composed of dystrophin and associated proteins, is essential for maintaining muscle membrane integrity. The link between mutations in dystrophin and the devastating muscle failure of Duchenne’s muscular dystrophy (DMD) has been well established. Less well appreciated are the accompanying cognitive impairment and neuropsychiatric disorders also presented in many DMD patients, which suggest a wider role for dystrophin in membrane–cytoskeleton function. This study provides genetic evidence of a novel role for DYS-1/dystrophin in maintaining neural organization in Caenorhabditis elegans. This neuronal function is distinct from the established role of DYS-1/dystrophin in maintaining muscle integrity and regulating locomotion. SAX-7, an L1 cell adhesion molecule (CAM) homologue, and STN-2/γ-syntrophin also function to maintain neural integrity in C. elegans. This study provides biochemical data that show that SAX-7 associates with DYS-1 in an STN-2/γ-syntrophin–dependent manner. These results reveal a recruitment of L1CAMs to the DPC to ensure neural integrity is maintained.

scholarly journals picd-1, a gene that encodes CABIN1 domain-containing protein, interacts with pry-1/Axin to regulate multiple processes in Caenorhabditis elegans

2021 ◽  
Author(s):  
Avijit Mallick ◽  
Shane K. B. Taylor ◽  
Sakshi Mehta ◽  
Bhagwati P. Gupta
Keyword(s):  
Stress Response ◽  
Essential Role ◽  
Family Members ◽  
Transcriptome Profiling ◽  
Scaffolding Protein ◽  
Dependent Manner ◽  
C Elegans ◽  
Downstream Effectors ◽  
Cellular Components

ABSTRACTAXIN family members control diverse biological processes in eukaryotes. As a scaffolding protein, AXIN facilitates interactions between cellular components and provides specificity to signaling pathways. Despite its crucial roles in metazoans and discovery of a large number of family members, the mechanism of AXIN function is not very well understood. The C. elegans AXIN homolog PRY-1 provides a powerful tool to identify interacting genes and downstream effectors that function in a conserved manner to regulate AXIN-mediated signaling. Previous work demonstrated pry-1’s essential role in developmental processes such as reproductive system, seam cells, and a P lineage cell P11.p. More recently, our lab carried out a transcriptome profiling of pry-1 mutant and uncovered the essential role of the gene in lipid metabolism, stress response, and aging. In this study, we have extended the work on pry-1 by reporting a novel interacting gene picd-1 (pry-1-interacting CABIN1 domain containing). Our findings have revealed that picd-1 plays an essential role in C. elegans and is involved in several pry-1-mediated processes including regulation of stress response and lifespan maintenance. In support of this, picd-1 expression overlaps with pry-1 in multiple tissues throughout the lifespan of animals. Further experiments showed that picd-1 inhibits CREB-regulated transcriptional coactivator homolog CRTC-1 function, which promotes longevity in a calcineurin-dependent manner. These data provide evidence for an essential role of the CABIN1 domain protein PICD-1 in mediating PRY-1 signaling in C. elegans.

Escherichia coli tol and rcs genes participate in the complex network affecting curli synthesis

Microbiology ◽  
2005 ◽  
Vol 151 (7) ◽  
pp. 2487-2497 ◽  
Author(s):  
Anne Vianney ◽  
Grégory Jubelin ◽  
Sophie Renault ◽  
Corine Dorel ◽  
Philippe Lejeune ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Biofilm Formation ◽  
Membrane Integrity ◽  
Regulatory Proteins ◽  
Gram Negative Bacteria ◽  
Dependent Manner ◽  
Dominant Effect ◽  
Gram Negative ◽  
E Coli

Curli are necessary for the adherence of Escherichia coli to surfaces, and to each other, during biofilm formation, and the csgBA and csgDEFG operons are both required for their synthesis. A recent survey of gene expression in Pseudomonas aeruginosa biofilms has identified tolA as a gene activated in biofilms. The tol genes play a fundamental role in maintaining the outer-membrane integrity of Gram-negative bacteria. RcsC, the sensor of the RcsBCD phosphorelay, is involved, together with RcsA, in colanic acid capsule synthesis, and also modulates the expression of tolQRA and csgDEFG. In addition, the RcsBCD phosphorelay is activated in tol mutants or when Tol proteins are overexpressed. These results led the authors to investigate the role of the tol genes in biofilm formation in laboratory and clinical isolates of E. coli. It was shown that the adherence of cells was lowered in the tol mutants. This could be the result of a drastic decrease in the expression of the csgBA operon, even though the expression of csgDEFG was slightly increased under such conditions. It was also shown that the Rcs system negatively controls the expression of the two csg operons in an RcsA-dependent manner. In the tol mutants, activation of csgDEFG occurred via OmpR and was dominant upon repression by RcsB and RcsA, while these two regulatory proteins repressed csgBA through a dominant effect on the activator protein CsgD, thus affecting curli synthesis. The results demonstrate that the Rcs system, previously known to control the synthesis of the capsule and the flagella, is an additional component involved in the regulation of curli. Furthermore, it is shown that the defect in cell motility observed in the tol mutants depends on RcsB and RcsA.

scholarly journals Axin-mediated regulation of lifespan and muscle health in C. elegans involves AMPK-FOXO signaling

2020 ◽  
Author(s):  
Avijit Mallick ◽  
Ayush Ranawade ◽  
Bhagwati P Gupta
Keyword(s):  
Muscle Function ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Mitochondrial Morphology ◽  
Dependent Manner ◽  
C Elegans ◽  
Muscle Aging ◽  
Muscle Health ◽  
Multiple Signaling

SUMMARYAging is a significant risk factor for several diseases. Studies have uncovered multiple signaling pathways that modulate the process of aging including the Insulin/IGF-1 signaling (IIS). In C. elegans the key regulator of IIS is DAF-16/FOXO whose activity is regulated by phosphorylation. A major kinase involved in DAF-16-mediated lifespan extension is the AMPK catalytic subunit homolog, AAK-2. In this study, we demonstrate a novel role of PRY-1/Axin in AAK-2 activation to regulate DAF-16 function. The pry-1 transcriptome contains many genes associated with aging and muscle function. Consistent with this, pry-1 is strongly expressed in muscles and muscle-specific overexpression of pry-1 extends the lifespan, delays muscle aging, and improves mitochondrial morphology in DAF-16-dependent manner. Furthermore, PRY-1 is necessary for AAK-2 phosphorylation. Together, our data demonstrate a crucial role of PRY-1 in maintaining the lifespan and muscle health. Since muscle health declines with age, our study offers new possibilities to manipulate Axin function to delay muscle aging and improve lifespan.

scholarly journals The autophagy receptor p62/SQST-1 promotes proteostasis and longevity in C. elegans by inducing autophagy

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Caroline Kumsta ◽  
Jessica T. Chang ◽  
Reina Lee ◽  
Ee Phie Tan ◽  
Yongzhi Yang ◽  
...  
Keyword(s):  
Heat Shock ◽  
Stress Responses ◽  
Dependent Manner ◽  
Selective Autophagy ◽  
C Elegans ◽  
Proteotoxic Stress ◽  
Autophagy Induction ◽  
The Impact ◽  
Lifespan Regulation

AbstractAutophagy can degrade cargos with the help of selective autophagy receptors such as p62/SQSTM1, which facilitates the degradation of ubiquitinated cargo. While the process of autophagy has been linked to aging, the impact of selective autophagy in lifespan regulation remains unclear. We have recently shown in Caenorhabditis elegans that transcript levels of sqst-1/p62 increase upon a hormetic heat shock, suggesting a role of SQST-1/p62 in stress response and aging. Here, we find that sqst-1/p62 is required for hormetic benefits of heat shock, including longevity, improved neuronal proteostasis, and autophagy induction. Furthermore, overexpression of SQST-1/p62 is sufficient to induce autophagy in distinct tissues, extend lifespan, and improve the fitness of mutants with defects in proteostasis in an autophagy-dependent manner. Collectively, these findings illustrate that increased expression of a selective autophagy receptor is sufficient to induce autophagy, enhance proteostasis and extend longevity, and demonstrate an important role for sqst-1/p62 in proteotoxic stress responses.

scholarly journals MiR-124 synergism with ELAVL3 enhances target gene expression to promote neuronal maturity

2020 ◽  
Author(s):  
Ya-Lin Lu ◽  
Yangjian Liu ◽  
Matthew J. McCoy ◽  
Andrew S. Yoo
Keyword(s):  
Gene Expression ◽  
Mirna Target ◽  
Target Gene ◽  
Target Genes ◽  
Dependent Manner ◽  
Neuronal Function ◽  
Mirna Target Gene ◽  
Target Gene Expression ◽  
Human Neurons

SummaryNeuron-enriched microRNAs (miRNAs), miR-9/9* and miR-124 (miR-9/9*-124), direct cell fate switching of human fibroblasts to neurons when ectopically expressed by repressing anti-neurogenic genes. How these miRNAs function after the onset of the transcriptome switch to a neuronal fate remains unclear. Here, we identified direct targets of miRNAs by Argonaute (AGO) HITS-CLIP as reprogramming cells activate the neuronal program and reveal the role of miR-124 that directly promotes the expression of its target genes associated with neuronal development and function. The mode of miR-124 as a positive regulator is determined by a neuron-enriched RNA-binding protein, ELAVL3, that interacts with AGO and binds target transcripts, whereas the non-neuronal ELAVL1 counterpart fails to elevate the miRNA-target gene expression. Although existing literature indicate that miRNA-ELAVL1 interaction can result in either target gene upregulation or downregulation in a context-dependent manner, we specifically identified neuronal ELAVL3 as the driver for miRNA target gene upregulation in neurons. In primary human neurons, repressing miR-124 and ELAVL3 led to the downregulation of genes involved in neuronal function and process outgrowth, and cellular phenotypes of reduced inward currents and neurite outgrowth. Results from our study support the role of miR-124 promoting neuronal function through positive regulation of its target genes.

scholarly journals Inflammation in Duchenne Muscular Dystrophy–Exploring the Role of Neutrophils in Muscle Damage and Regeneration

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1366
Author(s):  
Ankita Tulangekar ◽  
Tamar E. Sztal
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Damage ◽  
Tissue Injury ◽  
Dystrophin Gene ◽  
Neuromuscular Disorder ◽  
Muscle Membrane ◽  
Dystrophin Protein ◽  
Pro Inflammatory Cytokines

Duchenne muscular dystrophy (DMD) is a severe and progressive, X-linked, neuromuscular disorder caused by mutations in the dystrophin gene. In DMD, the lack of functional dystrophin protein makes the muscle membrane fragile, leaving the muscle fibers prone to damage during contraction. Muscle degeneration in DMD patients is closely associated with a prolonged inflammatory response, and while this is important to stimulate regeneration, inflammation is also thought to exacerbate muscle damage. Neutrophils are one of the first immune cells to be recruited to the damaged muscle and are the first line of defense during tissue injury or infection. Neutrophils can promote inflammation by releasing pro-inflammatory cytokines and compounds, including myeloperoxidase (MPO) and neutrophil elastase (NE), that lead to oxidative stress and are thought to have a role in prolonging inflammation in DMD. In this review, we provide an overview of the roles of the innate immune response, with particular focus on mechanisms used by neutrophils to exacerbate muscle damage and impair regeneration in DMD.

scholarly journals Significance of 14-3-3 Self-Dimerization for Phosphorylation-dependent Target Binding

2003 ◽  
Vol 14 (11) ◽  
pp. 4721-4733 ◽  
Author(s):  
Ying H. Shen ◽  
Jakub Godlewski ◽  
Agnieszka Bronisz ◽  
Jun Zhu ◽  
Michael J. Comb ◽  
...  
Keyword(s):  
Significant Role ◽  
Specific Antibody ◽  
Binding Motif ◽  
Dependent Manner ◽  
Phosphorylated Proteins ◽  
Associated Proteins ◽  
Target Binding ◽  
Eukaryotic Organisms

14-3-3 proteins via binding serine/threonine-phosphorylated proteins regulate diverse intracellular processes in all eukaryotic organisms. Here, we examine the role of 14-3-3 self-dimerization in target binding, and in the susceptibility of 14-3-3 to undergo phosphorylation. Using a phospho-specific antibody developed against a degenerated mode-1 14-3-3 binding motif (RSxpSxP), we demonstrate that most of the 14-3-3-associated proteins in COS-7 cells are phosphorylated on sites that react with this antibody. The binding of these phosphoproteins depends on 14-3-3 dimerization, inasmuch as proteins associated in vivo with a monomeric 14-3-3 form are not recognized by the phospho-specific antibody. The role of 14-3-3 dimerization in the phosphorylation-dependent target binding is further exemplified with two well-defined 14-3-3 targets, Raf and DAF-16. Raf and DAF-16 can bind both monomeric and dimeric 14-3-3; however, whereas phosphorylation of specific Raf and DAF-16 sites is required for binding to dimeric 14-3-3, binding to monomeric 14-3-3 forms is entirely independent of Raf and DAF-16 phosphorylation. We also find that dimerization diminishes 14-3-3 susceptibility to phosphorylation. These findings establish a significant role of 14-3-3 dimerization in its ability to bind targets in a phosphorylation-dependent manner and point to a mechanism in which 14-3-3 phosphorylation and dimerization counterregulate each other.

Role of dimethylsulfoniopropionate as an osmoprotectant following gradual salinity shifts in the sea-ice diatom Fragilariopsis cylindrus

2016 ◽  
Vol 13 (2) ◽  
pp. 181 ◽  
Author(s):  
Barbara R. Lyon ◽  
Jennifer M. Bennett-Mintz ◽  
Peter A. Lee ◽  
Michael G. Janech ◽  
Giacomo R. DiTullio
Keyword(s):  
Sea Ice ◽  
Environmental Gradients ◽  
Global Climate ◽  
Membrane Integrity ◽  
Polar Regions ◽  
Dependent Manner ◽  
Physiological Changes ◽  
Fragilariopsis Cylindrus ◽  
Ice Conditions

Environmental context Dimethylsulfoniopropionate (DMSP), a small sulfur compound biosynthesised by algae, plays an important role in global climate, particularly in polar regions. We investigated salinity effects on DMSP levels, and provide the first experimental measurements of DMSP and associated physiological changes in a polar diatom across to a range of gradual salinity shifts representative of sea-ice conditions. Quantitative estimates of DMSP in polar diatoms following salinity changes will facilitate new mathematical models to predict seasonal responses and reactions to climate change. Abstract Although extreme environmental gradients within sea-ice have been proposed to stimulate dimethylsulfoniopropionate (DMSP) accumulation in diatoms, a taxa whose temperate counterparts show relatively low concentrations, this has yet to be experimentally validated across a range of salinities representative of sea-ice conditions. The present study examined changes in DMSP concentrations in the widespread polar diatom Fragilariopsis cylindrus in response to gradual salinity shifts representative of those encountered during sea-ice formation and melt. DMSP concentrations were elevated up to 127% in 70-salinity cultures. Low-salinity shifts decreased intracellular DMSP concentrations in a gradient-dependent manner that suggests DMSP recycling rather than release under milder hyposalinity shifts. Permeable membranes were detected in ~45% of 10-salinity cells; therefore, loss of membrane integrity may only partially explain DMSP release in the lowest-salinity group. Growth rates, photosynthetic efficiency of photosystem II and reactive oxygen species detection indicated only partial impairment by salinity stress in this organism. Thus, experimental evidence supports the role of DMSP as a compatible solute in the acclimation of a sea-ice diatom across large salinity gradients and measurements of associated physiological changes will improve interpretation of environmental measurements.

scholarly journals Regulated distribution of mitochondria in touch receptor neurons of C. elegans influences touch response

2020 ◽  
Author(s):  
Anjali Awasthi ◽  
Souvik Modi ◽  
Sneha Hegde ◽  
Anusheela Chatterjee ◽  
Sudip Mondal ◽  
...  
Keyword(s):  
Molecular Motors ◽  
Neuronal Function ◽  
Mitochondrial Density ◽  
Neuronal Process ◽  
C Elegans ◽  
Touch Receptor Neurons ◽  
Touch Response ◽  
Receptor Neurons ◽  
Touch Receptor Neuron

AbstractDensity of mitochondria and their localization at specific sub-cellular regions of the neurons is regulated by molecular motors, their adaptors and the cytoskeleton. However, the regulation of the mitochondrial density, the positioning of mitochondria along the neuronal process and the role of axonal mitochondria in neuronal function remain poorly understood. This study shows that the density of mitochondria in C. elegans touch receptor neuron processes remains constant through development. Simulations show that mitochondrial positioning along parts of the neuronal process that are devoid of synapses is regulated. Additionally, we also demonstrate that axonal mitochondria are necessary for maintaining touch responsiveness.

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