scholarly journals Open syntaxin overcomes synaptic transmission defects in diverse C. elegans exocytosis mutants

2020 ◽  
Author(s):  
Chi-Wei Tien ◽  
Bin Yu ◽  
Mengjia Huang ◽  
Karolina P. Stepien ◽  
Kyoko Sugita ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Neurotransmitter Release ◽  
Alpha Subunit ◽  
Specific Function ◽  
Wild Type ◽  
C Elegans ◽  
Closed Conformation ◽  
Disease States ◽  
Wide Range ◽  
Liposome Fusion

SummaryAssembly of SNARE complexes that mediate neurotransmitter release requires opening of a ‘closed’ conformation of UNC-64/syntaxin. Rescue of unc-13/Munc13 phenotypes by overexpressed open UNC-64/syntaxin suggested a specific function of UNC-13/Munc13 in opening UNC-64/ syntaxin. Here, we revisit the effects of open unc-64/syntaxin by generating knockin (KI) worms. The KI animals exhibited enhanced spontaneous and evoked exocytosis compared to wild-type animals. Unexpectedly, the open syntaxin KI partially suppressed exocytosis defects of various mutants, including snt-1/synaptotagmin, unc-2/P/Q/N-type Ca2+ channel alpha-subunit, and unc-31/CAPS in addition to unc-13/Munc13 and unc-10/RIM, and enhanced exocytosis in tom-1/Tomosyn mutants. However, open syntaxin aggravated the defects of unc-18/Munc18 mutants. Correspondingly, open syntaxin partially bypasses the requirement of Munc13 but not Munc18 for liposome fusion. Our results show that facilitating opening of syntaxin enhances exocytosis in a wide range of genetic backgrounds, and may provide a general means to enhance synaptic transmission in normal and disease states.

scholarly journals Open syntaxin overcomes exocytosis defects of diverse mutants in C. elegans

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Chi-Wei Tien ◽  
Bin Yu ◽  
Mengjia Huang ◽  
Karolina P. Stepien ◽  
Kyoko Sugita ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Neurotransmitter Release ◽  
Alpha Subunit ◽  
Specific Function ◽  
C Elegans ◽  
Closed Conformation ◽  
Disease States ◽  
Wide Range ◽  
Mutant Phenotypes ◽  
Liposome Fusion

Abstract Assembly of SNARE complexes that mediate neurotransmitter release requires opening of a ‘closed’ conformation of UNC-64/syntaxin. Rescue of unc-13/Munc13 mutant phenotypes by overexpressed open UNC-64/syntaxin suggested a specific function of UNC-13/Munc13 in opening UNC-64/ syntaxin. Here, we revisit the effects of open unc-64/syntaxin by generating knockin (KI) worms. The KI animals exhibit enhanced spontaneous and evoked exocytosis compared to WT animals. Unexpectedly, the open syntaxin KI partially suppresses exocytosis defects of various mutants, including snt-1/synaptotagmin, unc-2/P/Q/N-type Ca2+ channel alpha-subunit and unc-31/CAPS, in addition to unc-13/Munc13 and unc-10/RIM, and enhanced exocytosis in tom-1/Tomosyn mutants. However, open syntaxin aggravates the defects of unc-18/Munc18 mutants. Correspondingly, open syntaxin partially bypasses the requirement of Munc13 but not Munc18 for liposome fusion. Our results show that facilitating opening of syntaxin enhances exocytosis in a wide range of genetic backgrounds, and may provide a general means to enhance synaptic transmission in normal and disease states.

scholarly journals Melatonin promotes sleep by activating the BK channel in C. elegans

2020 ◽  
Vol 117 (40) ◽  
pp. 25128-25137
Author(s):  
Longgang Niu ◽  
Yan Li ◽  
Pengyu Zong ◽  
Ping Liu ◽  
Yuan Shui ◽  
...  
Keyword(s):  
G Protein ◽  
Neurotransmitter Release ◽  
Expression System ◽  
Molecular Target ◽  
Bk Channel ◽  
G Protein Coupled Receptors ◽  
Wild Type ◽  
Heterologous Expression System ◽  
C Elegans ◽  
G Protein Coupled

Melatonin (Mel) promotes sleep through G protein-coupled receptors. However, the downstream molecular target(s) is unknown. We identified the Caenorhabditis elegans BK channel SLO-1 as a molecular target of the Mel receptor PCDR-1-. Knockout of pcdr-1, slo-1, or homt-1 (a gene required for Mel synthesis) causes substantially increased neurotransmitter release and shortened sleep duration, and these effects are nonadditive in double knockouts. Exogenous Mel inhibits neurotransmitter release and promotes sleep in wild-type (WT) but not pcdr-1 and slo-1 mutants. In a heterologous expression system, Mel activates the human BK channel (hSlo1) in a membrane-delimited manner in the presence of the Mel receptor MT1 but not MT2. A peptide acting to release free Gβγ also activates hSlo1 in a MT1-dependent and membrane-delimited manner, whereas a Gβλ inhibitor abolishes the stimulating effect of Mel. Our results suggest that Mel promotes sleep by activating the BK channel through a specific Mel receptor and Gβλ.

scholarly journals Multidimensional phenotyping predicts lifespan and quantifies health in C. elegans

2019 ◽  
Author(s):  
Céline N. Martineau ◽  
André E. X. Brown ◽  
Patrick Laurent
Keyword(s):  
Simple Model ◽  
Objective Measure ◽  
Quantitative Model ◽  
Model Organisms ◽  
Wild Type ◽  
Data Set ◽  
C Elegans ◽  
Wide Range ◽  
Initial Hypothesis

AbstractAgeing affects a wide range of phenotypes at all scales, but an objective measure of ageing remains challenging, even in simple model organisms. We assumed that a wide range of phenotypes at the organismal scale rather than a limited number of biomarkers of ageing would best describe the ageing process. Hundreds of morphological, postural and behavioural features are extracted at once from high resolutions videos. A quantitative model using this multi-parametric dataset can predict the biological age and lifespan of individual C. elegans. We show that the quality of predictions on a held-out data set increases with the number of features added to the model, supporting our initial hypothesis. Despite the large diversity of ageing mechanisms, including stochastic insults, our results highlight a robust ageing trajectory, but variable ageing rates along that trajectory. We show that healthspan, which we defined as the range of abilities of the animals, is correlated to lifespan in wild-type worms.

scholarly journals Monsters in the uterus: A parthenogenetic quasi-program causes teratoma-like tumors during aging in wild-type C.elegans

2017 ◽  
Author(s):  
Hongyuan Wang ◽  
Yuan Zhao ◽  
Marina Ezcurra ◽  
Ann F. Gilliat ◽  
Josephine Hellberg ◽  
...  
Keyword(s):  
Sperm Production ◽  
Wild Type ◽  
C Elegans ◽  
Cellular Hypertrophy ◽  
Bacterial Proliferation ◽  
Tumor Onset ◽  
Uterine Tumors ◽  
Starting Point ◽  
Wide Range ◽  
Type Gene

AbstractMany diseases whose frequency increases with advancing age are caused by aging (senescence), but the mechanisms of senescence remain poorly understood. According to G.C. Williams and M.V. Blagosklonny, a major etiological determinant of senescence is late-life, wild-type gene action and non-adaptive execution of biological programs (or quasi-programs). These generate a wide range of senescent pathologies causing illness and death. Here we investigate the etiology of a prominent senescent pathology in the nematode C. elegans, uterine tumors, in the light of the Williams Blagosklonny theory. Uterine tumors develop from unfertilized, immature oocytes which execute incomplete embryogenetic programs. This includes extensive endomitosis, leading to formation of chromatin masses and cellular hypertrophy. The starting point of pathogenesis is exhaustion of sperm stocks. The timing of this transition between program and quasi-program can be altered by blocking sperm production (causing earlier tumors) or supplying additional sperm by mating (delaying tumor onset). Other pathophysiological determinants are yolk consumption by tumors, and bacterial proliferation within tumors. Uterine tumors resemble mammalian ovarian teratomas (tera, Greek: monster) in that both develop from oocytes that fail to mature after meiosis I, and both are the result of quasi-programs. Moreover, older but not younger uterine tumors show expression of markers of later embryogenesis, i.e. are teratoma-like. These results show how uterine tumors in C. elegans form as the result of run-on of embryogenetic quasi-programs. They also suggest fundamental etiological equivalence between teratoma and some forms of senescent pathology, insofar as both are caused by quasi-programs.

scholarly journals Contribution of EAG to excitability and potassium currents in Drosophila larval motoneurons

2012 ◽  
Vol 107 (10) ◽  
pp. 2660-2671 ◽  
Author(s):  
Subhashini Srinivasan ◽  
Kimberley Lance ◽  
Richard B. Levine
Keyword(s):  
Neurotransmitter Release ◽  
Nerve Terminals ◽  
Spontaneous Firing ◽  
Wild Type ◽  
Voltage Gated ◽  
Larval Muscle ◽  
Whole Cell Patch Clamp ◽  
Wide Range ◽  
Functional Regulation

Diversity in the expression of K+ channels among neurons allows a wide range of excitability, growth, and functional regulation. Ether-à-go-go (EAG), a voltage-gated K+ channel, was first characterized in Drosophila mutants by spontaneous firing in nerve terminals and enhanced neurotransmitter release. Although diverse functions have been ascribed to this protein, its role within neurons remains poorly understood. The aim of this study was to characterize the function of EAG in situ in Drosophila larval motoneurons. Whole cell patch-clamp recordings performed from the somata revealed a decrease in IAv and IKv K+ currents in eag mutants and with targeted eag RNAi expression. Spontaneous spike-like events were observed in eag mutants but absent in wild-type motoneurons. Thus our results provide evidence that EAG represents a unique K+ channel contributing to multiple K+ currents in motoneurons helping to regulate excitability, consistent with previous observations in the Drosophila larval muscle.

The Effect of Mianserin on Lifespan of Caenorhabditis elegans is Abolished by Glucose

2021 ◽  
Vol 13 ◽  
Author(s):  
Abdullah Almotayri ◽  
Jency Thomas ◽  
Mihiri Munasinghe ◽  
Markandeya Jois
Keyword(s):  
Caenorhabditis Elegans ◽  
Scaffolding Protein ◽  
Lifespan Extension ◽  
Wild Type ◽  
E Coli ◽  
C Elegans ◽  
Risk Of Death ◽  
Increased Risk ◽  
Antidepressant Use ◽  
Extension Effect

Background: The antidepressant mianserin has been shown to extend the lifespan of Caenorhabditis elegans (C. elegans), a well-established model organism used in aging research. The extension of lifespan in C. elegans was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegans in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin. Objective: To investigate the effect of glucose added to the diet of C. elegans on the lifespan-extension effect of mianserin. Methods: Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 μM mianserin, (G) 73 mM glucose, and (M50G) 50 μM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test. Results: Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin. Conclusion: The addition of glucose to the diet of C. elegans abolishes the lifespan-extension effects of mianserin.

scholarly journals The NALCN Channel Regulator UNC-80 Functions in a Subset of Interneurons To Regulate Caenorhabditis elegans Reversal Behavior

2019 ◽  
Vol 10 (1) ◽  
pp. 199-210 ◽  
Author(s):  
Chuanman Zhou ◽  
Jintao Luo ◽  
Xiaohui He ◽  
Qian Zhou ◽  
Yunxia He ◽  
...  
Keyword(s):  
Plant Hormone ◽  
Neuronal Excitability ◽  
Resting Membrane Potential ◽  
Loss Of Function ◽  
Wild Type ◽  
C Elegans ◽  
Link Type ◽  
Complex Functions ◽  
And Function ◽  
Multiple Loss

NALCN (Na+leak channel, non-selective) is a conserved, voltage-insensitive cation channel that regulates resting membrane potential and neuronal excitability. UNC79 and UNC80 are key regulators of the channel function. However, the behavioral effects of the channel complex are not entirely clear and the neurons in which the channel functions remain to be identified. In a forward genetic screen for C. elegans mutants with defective avoidance response to the plant hormone methyl salicylate (MeSa), we isolated multiple loss-of-function mutations in unc-80 and unc-79. C. elegans NALCN mutants exhibited similarly defective MeSa avoidance. Interestingly, NALCN, unc-80 and unc-79 mutants all showed wild type-like responses to other attractive or repelling odorants, suggesting that NALCN does not broadly affect odor detection or related forward and reversal behaviors. To understand in which neurons the channel functions, we determined the identities of a subset of unc-80-expressing neurons. We found that unc-79 and unc-80 are expressed and function in overlapping neurons, which verified previous assumptions. Neuron-specific transgene rescue and knockdown experiments suggest that the command interneurons AVA and AVE and the anterior guidepost neuron AVG can play a sufficient role in mediating unc-80 regulation of the MeSa avoidance. Though primarily based on genetic analyses, our results further imply that MeSa might activate NALCN by direct or indirect actions. Altogether, we provide an initial look into the key neurons in which the NALCN channel complex functions and identify a novel function of the channel in regulating C. elegans reversal behavior through command interneurons.

scholarly journals Sperm Competition in the Absence of Fertilization in Caenorhabditis elegans

Genetics ◽  
1999 ◽  
Vol 152 (1) ◽  
pp. 201-208 ◽  
Author(s):  
Andrew Singson ◽  
Katherine L Hill ◽  
Steven W L’Hernault
Keyword(s):  
Caenorhabditis Elegans ◽  
Sperm Competition ◽  
Sperm Function ◽  
Sperm Precedence ◽  
Wild Type ◽  
Nematode Caenorhabditis Elegans ◽  
C Elegans ◽  
Normal Sperm ◽  
Self Fertilization ◽  
Competition Assays

Abstract Hermaphrodite self-fertilization is the primary mode of reproduction in the nematode Caenorhabditis elegans. However, when a hermaphrodite is crossed with a male, nearly all of the oocytes are fertilized by male-derived sperm. This sperm precedence during reproduction is due to the competitive superiority of male-derived sperm and results in a functional suppression of hermaphrodite self-fertility. In this study, mutant males that inseminate fertilization-defective sperm were used to reveal that sperm competition within a hermaphrodite does not require successful fertilization. However, sperm competition does require normal sperm motility. Additionally, sperm competition is not an absolute process because oocytes not fertilized by male-derived sperm can sometimes be fertilized by hermaphrodite-derived sperm. These results indicate that outcrossed progeny result from a wild-type cross because male-derived sperm are competitively superior and hermaphrodite-derived sperm become unavailable to oocytes. The sperm competition assays described in this study will be useful in further classifying the large number of currently identified mutations that alter sperm function and development in C. elegans.

Streblus asper Lour. exerts MAPK and SKN-1 mediated anti-aging, anti-photoaging activities and imparts neuroprotection by ameliorating Aβ in Caenorhabditis elegans

2021 ◽  
pp. 1-17
Author(s):  
Mani Iyer Prasanth ◽  
James Michael Brimson ◽  
Dicson Sheeja Malar ◽  
Anchalee Prasansuklab ◽  
Tewin Tencomnao
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Stress Resistance ◽  
Vital Role ◽  
Transgenic Strain ◽  
Wild Type ◽  
Neuroprotective Effects ◽  
C Elegans ◽  
Streblus Asper

BACKGROUND: Streblus asper Lour., has been reported to have anti-aging and neuroprotective efficacies in vitro. OBJECTIVE: To analyze the anti-aging, anti-photoaging and neuroprotective efficacies of S. asper in Caenorhabditis elegans. METHODS: C. elegans (wild type and gene specific mutants) were treated with S. asper extract and analyzed for lifespan and other health benefits through physiological assays, fluorescence microscopy, qPCR and Western blot. RESULTS: The plant extract was found to increase the lifespan, reduce the accumulation of lipofuscin and modulate the expression of candidate genes. It could extend the lifespan of both daf-16 and daf-2 mutants whereas the pmk-1 mutant showed no effect. The activation of skn-1 was observed in skn-1::GFP transgenic strain and in qPCR expression. Further, the extract can extend the lifespan of UV-A exposed nematodes along with reducing ROS levels. Additionally, the extract also extends lifespan and reduces paralysis in Aβ transgenic strain, apart from reducing Aβ expression. CONCLUSIONS: S. asper was able to extend the lifespan and healthspan of C. elegans which was independent of DAF-16 pathway but dependent on SKN-1 and MAPK which could play a vital role in eliciting the anti-aging, anti-photoaging and neuroprotective effects, as the extract could impart oxidative stress resistance and neuroprotection.

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