scholarly journals Redox signaling modulates Rho activity and tissue contractility in the C. elegans spermatheca

2019 ◽  
Author(s):  
Charlotte A. Kelley ◽  
Sasha De Henau ◽  
Liam Bell ◽  
Tobias B. Dansen ◽  
Erin J. Cram
Keyword(s):  
Hydrogen Peroxide ◽  
Active Site ◽  
Myoepithelial Cells ◽  
Redox Signaling ◽  
Small Gtpase ◽  
C Elegans ◽  
Hydrogen Peroxide Treatment ◽  
Fine Tune ◽  
Contractile Tissue

AbstractActomyosin based contractility in smooth muscle and non-muscle cells is regulated by signaling through the small GTPase Rho and by calcium-activated pathways. We use the myoepithelial cells of the Caenorhabditis elegans spermatheca to study the mechanisms of coordinated myosin activation in vivo. Here, we demonstrate that redox signaling regulates RHO-1/Rho activity in this contractile tissue. Exogenous hydrogen peroxide treatment decreases spermathecal contractility by inhibiting RHO-1, which is mediated through a conserved cysteine in its active site (C20). Further, we identify a gradient of oxidation across the spermathecal tissue, which is regulated by the cytosolic superoxide dismutase, SOD-1. SOD-1 functions in the Rho pathway to inhibit RHO-1 through oxidation of C20. Our results suggest that SOD-1 functions to regulate the redox environment and to fine-tune Rho activity across the spermatheca.

scholarly journals Novel and Converging Ways of NOX2 and SOD3 in Trafficking and Redox Signaling in Macrophages

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 172
Author(s):  
Steen Vang Petersen ◽  
Nanna Bach Poulsen ◽  
Cecilie Linneberg Matthiesen ◽  
Frederik Vilhardt
Keyword(s):  
Hydrogen Peroxide ◽  
Membrane Trafficking ◽  
Spatial Organization ◽  
Redox Signaling ◽  
Small Gtpase ◽  
Paracrine Signaling ◽  
Tissue Macrophage ◽  
Storage Vesicles ◽  
Superoxide Dismutase 3 ◽  
Macrophage Populations

Macrophages and related tissue macrophage populations use the classical NADPH oxidase (NOX2) for the regulated production of superoxide and derived oxidants for pathogen combat and redox signaling. With an emphasis on macrophages, we discuss how sorting into secretory storage vesicles, agonist-responsive membrane trafficking, and segregation into sphingolipid and cholesterol-enriched microdomains (lipid rafts) determine the subcellular distribution and spatial organization of NOX2 and superoxide dismutase-3 (SOD3). We discuss how inflammatory activation of macrophages, in part through small GTPase Rab27A/B regulation of the secretory compartments, mediates the coalescence of these two proteins on the cell surface to deliver a focalized hydrogen peroxide output. In interplay with membrane-embedded oxidant transporters and redox sensitive target proteins, this arrangement allows for the autocrine and paracrine signaling, which govern macrophage activation states and transcriptional programs. By discussing examples of autocrine and paracrine redox signaling, we highlight why formation of spatiotemporal microenvironments where produced superoxide is rapidly converted to hydrogen peroxide and conveyed immediately to reach redox targets in proximal vicinity is required for efficient redox signaling. Finally, we discuss the recent discovery of macrophage-derived exosomes as vehicles of NOX2 holoenzyme export to other cells.

scholarly journals Redox signaling modulates Rho activity and tissue contractility in the Caenorhabditis elegans spermatheca

2020 ◽  
Vol 31 (14) ◽  
pp. 1486-1497 ◽  
Author(s):  
Charlotte A. Kelley ◽  
Sasha De Henau ◽  
Liam Bell ◽  
Tobias B. Dansen ◽  
Erin J. Cram
Keyword(s):  
Superoxide Dismutase ◽  
Caenorhabditis Elegans ◽  
Redox Signaling ◽  
C Elegans ◽  
Contractile Tissue

H2O2 modulates RHO-1/Rho activity in the contractile tissue of the C. elegans spermatheca. Both exogenous and endogenously generated H2O2 decrease spermathecal contractility by inhibition of RHO-1 through oxidation of Cys 20. Regulation of H2O2 levels in the spermatheca depends on the activity of the cytosolic superoxide dismutase SOD-1.

scholarly journals The Amyloid Precursor-like Protein APL-1 Regulates Axon Regeneration

2018 ◽  
Author(s):  
Lewie Zeng ◽  
Rachid El Bejjani ◽  
Marc Hammarlund
Keyword(s):  
Motor Neurons ◽  
Neuronal Development ◽  
Axon Regeneration ◽  
Neuronal Response ◽  
Small Gtpase ◽  
C Elegans ◽  
Protein Levels ◽  
Mature Neurons ◽  
And Function

AbstractMembers of the Amyloid Precursor Protein (APP) family have important functions during neuronal development. However, their physiological functions in the mature nervous system are not fully understood. Here we use the C. elegans GABAergic motor neurons to study the post-developmental function of the APP-like protein APL-1 in vivo. We find that apl-1 has minimum roles in the maintenance of gross neuron morphology and function. However, we show that apl-1 is an inhibitor of axon regeneration, acting on mature neurons to limit regrowth in response to injury. The small GTPase Rab6/RAB-6.2 also inhibits regeneration, and does so in part by maintaining protein levels of APL-1. To inhibit regeneration, APL-1 functions via the E2 domain of its ectodomain; the cytoplasmic tail, transmembrane anchoring, and the E1 domain are not required for this function. Our data defines a novel role for APL-1 in modulating the neuronal response to injury.

scholarly journals Myosin activity drives actomyosin bundle formation and organization in contractile cells of the Caenorhabditis elegans spermatheca

2017 ◽  
Vol 28 (14) ◽  
pp. 1937-1949 ◽  
Author(s):  
Alison C. E. Wirshing ◽  
Erin J. Cram
Keyword(s):  
Smooth Muscle ◽  
Caenorhabditis Elegans ◽  
Force Production ◽  
Myoepithelial Cells ◽  
Stress Fibers ◽  
C Elegans ◽  
Cell Stretch ◽  
Bundle Size ◽  
Contractile Cells

Stress fibers—contractile actomyosin bundles—are important for cellular force production and adaptation to physical stress and have been well studied within the context of cell migration. However, less is known about actomyosin bundle formation and organization in vivo and in specialized contractile cells, such as smooth muscle and myoepithelial cells. The Caenorhabditis elegans spermatheca is a bag-like organ of 24 myoepithelial cells that houses the sperm and is the site of fertilization. During ovulation, spermathecal cells are stretched by oocyte entry and then coordinately contract to expel the fertilized embryo into the uterus. Here we use four-dimensional confocal microscopy of live animals to observe changes to spermathecal actomyosin network organization during cell stretch and contraction. Oocyte entry is required to trigger cell contraction and concomitant production of parallel actomyosin bundles. Actomyosin bundle size, connectivity, spacing, and orientation are regulated by myosin activity. We conclude that myosin drives actomyosin bundle production and that myosin activity is tightly regulated during ovulation to produce an optimally organized actomyosin network in C. elegans spermathecae.

scholarly journals Global profiling of distinct cysteine redox forms reveals wide-ranging redox regulation in C. elegans

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jin Meng ◽  
Ling Fu ◽  
Keke Liu ◽  
Caiping Tian ◽  
Ziyun Wu ◽  
...  
Keyword(s):  
Redox Regulation ◽  
Mapk Pathway ◽  
Model Organism ◽  
Redox Signaling ◽  
P38 Map Kinase ◽  
Redox Biology ◽  
C Elegans ◽  
Protein Functions ◽  
Redox Forms

AbstractPost-translational changes in the redox state of cysteine residues can rapidly and reversibly alter protein functions, thereby modulating biological processes. The nematode C. elegans is an ideal model organism for studying cysteine-mediated redox signaling at a network level. Here we present a comprehensive, quantitative, and site-specific profile of the intrinsic reactivity of the cysteinome in wild-type C. elegans. We also describe a global characterization of the C. elegans redoxome in which we measured changes in three major cysteine redox forms after H2O2 treatment. Our data revealed redox-sensitive events in translation, growth signaling, and stress response pathways, and identified redox-regulated cysteines that are important for signaling through the p38 MAP kinase (MAPK) pathway. Our in-depth proteomic dataset provides a molecular basis for understanding redox signaling in vivo, and will serve as a valuable and rich resource for the field of redox biology.

scholarly journals FLN-1/Filamin is required to anchor the actomyosin cytoskeleton and for global organization of sub-cellular organelles in a contractile tissue

2020 ◽  
Author(s):  
Charlotte A. Kelley ◽  
Olivia Triplett ◽  
Samyukta Mallick ◽  
Kristopher Burkewitz ◽  
William B. Mair ◽  
...  
Keyword(s):  
Myoepithelial Cells ◽  
Cell Junctions ◽  
Tissue Loss ◽  
Linc Complex ◽  
Regular Array ◽  
C Elegans ◽  
Global Organization ◽  
Actomyosin Cytoskeleton ◽  
Contractile Tissue ◽  
Cellular Organelles

AbstractActomyosin networks are organized in space, direction, size, and connectivity to produce coordinated contractions across cells. We use the C. elegans spermatheca, a tube composed of contractile myoepithelial cells, to study how actomyosin structures are organized. FLN-1/filamin is required for the formation and stabilization of a regular array of parallel, contractile, actomyosin fibers in this tissue. Loss of fln-1 results in the detachment of actin fibers from the basal surface, which then accumulate along the cell junctions and are stabilized by spectrin. In addition, actin and myosin are captured at the nucleus by the linker of nucleoskeleton and cytoskeleton complex (LINC) complex, where they form large foci. Nuclear positioning and morphology, distribution of the endoplasmic reticulum and the mitochondrial network are also disrupted. These results demonstrate that filamin is required to prevent large actin bundle formation and detachment, to prevent excess nuclear localization of actin and myosin, and to ensure correct positioning of organelles.

scholarly journals Crystal Structure of CRN-4: Implications for Domain Function in Apoptotic DNA Degradation

2008 ◽  
Vol 29 (2) ◽  
pp. 448-457 ◽  
Author(s):  
Yu-Yuan Hsiao ◽  
Akihisa Nakagawa ◽  
Zhonghao Shi ◽  
Shohei Mitani ◽  
Ding Xue ◽  
...  
Keyword(s):  
Cell Death ◽  
Active Site ◽  
Structural Model ◽  
Active Form ◽  
Dna Degradation ◽  
Biochemical Properties ◽  
Chromosomal Dna ◽  
C Elegans ◽  
Cell Functions

ABSTRACT Cell death related nuclease 4 (CRN-4) is one of the apoptotic nucleases involved in DNA degradation in Caenorhabditis elegans. To understand how CRN-4 is involved in apoptotic DNA fragmentation, we analyzed CRN-4's biochemical properties, in vivo cell functions, and the crystal structures of CRN-4 in apo-form, Mn2+-bound active form, and Er3+-bound inactive form. CRN-4 is a dimeric nuclease with the optimal enzyme activity in cleaving double-stranded DNA in apoptotic salt conditions. Both mutational studies and the structures of the Mn2+-bound CRN-4 revealed the geometry of the functional nuclease active site in the N-terminal DEDDh domain. The C-terminal domain, termed the Zn-domain, contains basic surface residues ideal for nucleic acid recognition and is involved in DNA binding, as confirmed by deletion assays. Cell death analysis in C. elegans further demonstrated that both the nuclease active site and the Zn-domain are required for crn-4's function in apoptosis. Combining all of the data, we suggest a structural model where chromosomal DNA is bound at the Zn-domain and cleaved at the DEDDh nuclease domain in CRN-4 when the cell is undergoing apoptosis.

scholarly journals In Vivo Effects of Two In-Office Vital Tooth Bleaching Systems on Enamel Permeability

2021 ◽  
Vol 5 (4) ◽  
pp. 98
Author(s):  
Angelica Bertacci ◽  
Gianfranco Ulian ◽  
Daniele Moro ◽  
Stefano Chersoni ◽  
Giovanni Valdrè
Keyword(s):  
Hydrogen Peroxide ◽  
Surface Morphology ◽  
Tooth Enamel ◽  
Tooth Bleaching ◽  
Carbamide Peroxide ◽  
Tooth Sensitivity ◽  
Hydrogen Peroxide Treatment ◽  
Enamel Structure ◽  
The Aesthetic

Tooth bleaching is a common treatment for the amelioration of the aesthetic of discoloured teeth. In this context, there are two common approaches that employ concentrated solutions (30–40 wt.%) of either hydrogen peroxide or carbamide peroxide as bleaching agents. However, there is an ongoing debate on the possible adverse effects of these different treatments on tooth health, such as variation of the enamel structure, surface morphology, and chemistry, which also affect tooth sensitivity. In the present work, a study on the effect of the two bleaching agents, a 35 wt.% solution of hydrogen peroxide and a 30 wt.% solution of carbamide peroxide, on the permeability and surface morphology of enamel is reported. The investigation was carried out on replicas of incisors obtained after different treatment times and for several patients, employing scanning electron microscopy to study the morphological features of the treated teeth. The significance of the analytical study was corroborated by a statistical analysis of the results. The collected data suggest that hydrogen peroxide treatment increases the enamel permeability, and this could be related with tooth sensitivity, whereas the carbamide peroxide solution increases the formation of precipitates on the tooth enamel.

scholarly journals Rap2 and TNIK control Plexin-dependent tiled synaptic innervation in C. elegans

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Xi Chen ◽  
Akihiro CE Shibata ◽  
Ardalan Hendi ◽  
Mizuki Kurashina ◽  
Ethan Fortes ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Small Gtpase ◽  
Negative Regulator ◽  
Gtpase Activity ◽  
C Elegans ◽  
Receptor Interactions ◽  
Presynaptic Assembly ◽  
Intracellular Mechanisms

During development, neurons form synapses with their fate-determined targets. While we begin to elucidate the mechanisms by which extracellular ligand-receptor interactions enhance synapse specificity by inhibiting synaptogenesis, our knowledge about their intracellular mechanisms remains limited. Here we show that Rap2 GTPase (rap-2) and its effector, TNIK (mig-15), act genetically downstream of Plexin (plx-1) to restrict presynaptic assembly and to form tiled synaptic innervation in C. elegans. Both constitutively GTP- and GDP-forms of rap-2 mutants exhibit synaptic tiling defects as plx-1 mutants, suggesting that cycling of the RAP-2 nucleotide state is critical for synapse inhibition. Consistently, PLX-1 suppresses local RAP-2 activity. Excessive ectopic synapse formation in mig-15 mutants causes a severe synaptic tiling defect. Conversely, overexpression of mig-15 strongly inhibited synapse formation, suggesting that mig-15 is a negative regulator of synapse formation. These results reveal that subcellular regulation of small GTPase activity by Plexin shapes proper synapse patterning in vivo.

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