Ectocytosis prevents accumulation of ciliary cargo in C. elegans sensory neurons

Cilia are sensory organelles protruding from cell surfaces. Release of extracellular vesicles (EVs) from cilia was previously observed in mammals, Chlamydomonas, and in male Caenorhabditis elegans. Using the EV marker TSP-6 (an ortholog of mammalian CD9) and other ciliary receptors, we show that EVs are formed from ciliated sensory neurons in C. elegans hermaphrodites. Release of EVs is observed from two ciliary locations: the cilia tip and/or periciliary membrane compartment (PCMC). Outward budding of EVs from the cilia tip leads to their release into the environment. EVs’ budding from the PCMC is concomitantly phagocytosed by the associated glial cells. To maintain cilia composition, a tight regulation of cargo import and removal is achieved by the action of intra-flagellar transport (IFT). Unbalanced IFT due to cargo overexpression or mutations in the IFT machinery leads to local accumulation of ciliary proteins. Disposal of excess ciliary proteins via EVs reduces their local accumulation and exports them to the environment and/or to the glia associated to these ciliated neurons. We suggest that EV budding from cilia subcompartments acts as a safeguard mechanism to remove deleterious excess of ciliary material.

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Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases

Nature Communications ◽

10.1038/s41467-020-20269-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Mercedes M. Pérez-Jiménez ◽

José M. Monje-Moreno ◽

Ana María Brokate-Llanos ◽

Mónica Venegas-Calerón ◽

Alicia Sánchez-García ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Caenorhabditis Elegans ◽

Protein Aggregation ◽

Steroid Hormones ◽

Sensory Neurons ◽

Environmental Cues ◽

Steroid Sulfatase ◽

Loss Of Function ◽

C Elegans ◽

Age Related

AbstractAging and fertility are two interconnected processes. From invertebrates to mammals, absence of the germline increases longevity. Here we show that loss of function of sul-2, the Caenorhabditis elegans steroid sulfatase (STS), raises the pool of sulfated steroid hormones, increases longevity and ameliorates protein aggregation diseases. This increased longevity requires factors involved in germline-mediated longevity (daf-16, daf-12, kri-1, tcer-1 and daf-36 genes) although sul-2 mutations do not affect fertility. Interestingly, sul-2 is only expressed in sensory neurons, suggesting a regulation of sulfated hormones state by environmental cues. Treatment with the specific STS inhibitor STX64, as well as with testosterone-derived sulfated hormones reproduces the longevity phenotype of sul-2 mutants. Remarkably, those treatments ameliorate protein aggregation diseases in C. elegans, and STX64 also Alzheimer’s disease in a mammalian model. These results open the possibility of reallocating steroid sulfatase inhibitors or derivates for the treatment of aging and aging related diseases.

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Ultrasound neuro-modulation chip: activation of sensory neurons in Caenorhabditis elegans by surface acoustic waves

Lab on a Chip ◽

10.1039/c7lc00163k ◽

2017 ◽

Vol 17 (10) ◽

pp. 1725-1731 ◽

Cited By ~ 37

Author(s):

Wei Zhou ◽

Jingjing Wang ◽

Kaiyue Wang ◽

Bin Huang ◽

Lili Niu ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Sensory Neurons ◽

Acoustic Waves ◽

Surface Acoustic Waves ◽

C Elegans

We demonstrate an ultrasound neuro-modulation chip capable of activating neurons of the C. elegans directly.

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A cilia-mediated environmental input induces solitary behaviour in Caenorhabditis elegans and Pristionchus pacificus nematodes

Nematology ◽

10.1163/15685411-00003159 ◽

2018 ◽

Vol 20 (3) ◽

pp. 201-209 ◽

Cited By ~ 3

Author(s):

Eduardo Moreno ◽

Ralf J. Sommer

Keyword(s):

Caenorhabditis Elegans ◽

Social Behaviour ◽

Intraflagellar Transport ◽

Large Protein ◽

Pristionchus Pacificus ◽

C Elegans ◽

The Social ◽

Genes Encoding ◽

Social Behaviours ◽

Ciliated Neurons

Nematodes respond to a multitude of environmental cues. For example, the social behaviours clumping and bordering were described as a mechanism of hyperoxia avoidance in Caenorhabditis elegans and Pristionchus pacificus. A recent study in P. pacificus revealed a novel regulatory pathway that inhibits social behaviour in a response to an as yet unknown environmental cue. This environmental signal is recognised by ciliated neurons, as mutants defective in intraflagellar transport (IFT) proteins display social behaviours. The IFT machinery represents a large protein complex and many mutants in genes encoding IFT proteins are available in C. elegans. However, social phenotypes in C. elegans IFT mutants have never been reported. Here, we examined 15 previously isolated C. elegans IFT mutants and found that most of them showed strong social behaviour. These findings indicate conservation in the inhibitory mechanism of social behaviour between P. pacificus and C. elegans.

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C. elegans Ciliated Sensory Neurons Release Extracellular Vesicles that Function in Animal Communication

Current Biology ◽

10.1016/j.cub.2014.01.002 ◽

2014 ◽

Vol 24 (5) ◽

pp. 519-525 ◽

Cited By ~ 107

Author(s):

Juan Wang ◽

Malan Silva ◽

Leonard A. Haas ◽

Natalia S. Morsci ◽

Ken C.Q. Nguyen ◽

...

Keyword(s):

Extracellular Vesicles ◽

Sensory Neurons ◽

Animal Communication ◽

C Elegans

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The C. elegans septin genes, unc-59 and unc-61, are required for normal postembryonic cytokineses and morphogenesis but have no essential function in embryogenesis

Journal of Cell Science ◽

10.1242/jcs.113.21.3825 ◽

2000 ◽

Vol 113 (21) ◽

pp. 3825-3837 ◽

Cited By ~ 4

Author(s):

T.Q. Nguyen ◽

H. Sawa ◽

H. Okano ◽

J.G. White

Keyword(s):

Caenorhabditis Elegans ◽

Embryonic Development ◽

Sensory Neurons ◽

Leading Edge ◽

The Other ◽

Male Tail ◽

Genomic Database ◽

C Elegans ◽

Essential Function ◽

Normal Embryonic Development

Septins have been shown to play important roles in cytokinesis in diverse organisms ranging from yeast to mammals. In this study, we show that both the unc-59 and unc-61 loci encode Caenorhabditis elegans septins. Genomic database searches indicate that unc-59 and unc-61 are probably the only septin genes in the C. elegans genome. UNC-59 and UNC-61 localize to the leading edge of cleavage furrows and eventually reside at the midbody. Analysis of unc-59 and unc-61 mutants revealed that each septin requires the presence of the other for localization to the cytokinetic furrow. Surprisingly, unc-59 and unc-61 mutants generally have normal embryonic development; however, defects were observed in post-embryonic development affecting the morphogenesis of the vulva, male tail, gonad, and sensory neurons. These defects can be at least partially attributed to failures in post-embryonic cytokineses although our data also suggest other possible roles for septins. unc-59 and unc-61 double mutants show similar defects to each of the single mutants.

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Ectosome uptake by glia sculpts Caenorhabditis elegans sensory cilia

10.1101/2021.02.14.430969 ◽

2021 ◽

Author(s):

Adrià Razzauti ◽

Patrick Laurent

Keyword(s):

Caenorhabditis Elegans ◽

Cell Surface ◽

Glial Cells ◽

Intraflagellar Transport ◽

Membrane Receptors ◽

Sensory Function ◽

C Elegans ◽

Sensory Cilia

AbstractCilia are sensory organelles protruding from cell surface. A tight regulation of membrane receptors traffic in and out of cilia is achieved by the action of Intraflagellar Transport (IFT). Here, we show that ectosomes bud from a subset of C. elegans sensory cilia. Packing and disposal of ciliary receptors in ectosomes complement their retrieval by IFT. Mutations in ciliary retrieval genes increase export of the salt sensor GCY-22 from ASER neurons by ectosomes, preventing its accumulation in ASER cilia. Ectosomes are produced from two ciliary locations: cilia tip and/or cilia base. Ectosomes budding from cilia tip are released in the environment. Ectosomes produced from the cilia base are concomitantly phagocytosed by the associated glial cells. Although ectocytosis does not require glia to occur, ectosome phagocytosis by the contacting glia contributes to maintain cilia shape and sensory function. We suggest this coordinated neuron-glia interaction is required for proper cilia function.

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Ancestral roles of glia suggested by the nervous system of Caenorhabditis elegans

Neuron Glia Biology ◽

10.1017/s1740925x07000609 ◽

2007 ◽

Vol 3 (1) ◽

pp. 55-61 ◽

Cited By ~ 11

Author(s):

Maxwell G. Heiman ◽

Shai Shaham

Keyword(s):

Nervous System ◽

Caenorhabditis Elegans ◽

Glial Cell ◽

Glial Cells ◽

Cell Types ◽

Neuronal Morphology ◽

Sensory Organs ◽

Nematode Caenorhabditis Elegans ◽

C Elegans

AbstractThe nematode Caenorhabditis elegans has a simple nervous system with glia restricted primarily to sensory organs. Some of the activities that would be provided by glia in the mammalian nervous system are either absent or provided by non-glial cell types in C. elegans, with only a select set of mammalian glial activities being similarly provided by specialized glial cells in this animal. These observations suggest that ancestral roles of glia may be to modulate neuronal morphology and neuronal sensitivity in sensory organs.

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Regulatory changes in two chemoreceptor genes contribute to a Caenorhabditis elegans QTL for foraging behavior

eLife ◽

10.7554/elife.21454 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 39

Author(s):

Joshua S Greene ◽

May Dobosiewicz ◽

Rebecca A Butcher ◽

Patrick T McGrath ◽

Cornelia I Bargmann

Keyword(s):

Caenorhabditis Elegans ◽

Foraging Behavior ◽

Sensory Neurons ◽

Exploratory Behavior ◽

Adaptive Variation ◽

C Elegans ◽

Regulatory Changes ◽

Naturally Occurring ◽

Genome Wide ◽

Natural Isolates

Natural isolates of C. elegans differ in their sensitivity to pheromones that inhibit exploratory behavior. Previous studies identified a QTL for pheromone sensitivity that includes alternative alleles of srx-43, a chemoreceptor that inhibits exploration through its activity in ASI sensory neurons. Here we show that the QTL is multigenic and includes alternative alleles of srx-44, a second chemoreceptor gene that modifies pheromone sensitivity. srx-44 either promotes or inhibits exploration depending on its expression in the ASJ or ADL sensory neurons, respectively. Naturally occurring pheromone insensitivity results in part from previously described changes in srx-43 expression levels, and in part from increased srx-44 expression in ASJ, which antagonizes ASI and ADL. Antagonism between the sensory neurons results in cellular epistasis that is reflected in their transcription of insulin genes that regulate exploration. These results and genome-wide evidence suggest that chemoreceptor genes may be preferred sites of adaptive variation in C. elegans.

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Regulation of Satiety Quiescence by Neuropeptide Signaling in Caenorhabditis elegans

Frontiers in Neuroscience ◽

10.3389/fnins.2021.678590 ◽

2021 ◽

Vol 15 ◽

Author(s):

Mei Makino ◽

Enkhjin Ulzii ◽

Riku Shirasaki ◽

Jeongho Kim ◽

Young-Jai You

Keyword(s):

Caenorhabditis Elegans ◽

Sensory Neurons ◽

Significant Role ◽

Sleep Cycle ◽

Over Expression ◽

C Elegans ◽

Feeding Cycle ◽

Cgmp Signaling ◽

Key Aspects ◽

Tgfβ Pathway

Sleep and metabolism are interconnected homeostatic states; the sleep cycle can be entrained by the feeding cycle, and perturbation of the sleep often results in dysregulation in metabolism. However, the neuro-molecular mechanism by which metabolism regulates sleep is not fully understood. We investigated how metabolism and feeding regulate sleep using satiety quiescence behavior as a readout in Caenorhabditis elegans, which shares certain key aspects of postprandial sleep in mammals. From an RNA interference-based screen of two neuropeptide families, RFamide-related peptides (FLPs) and insulin-like peptides (INSs), we identified flp-11, known to regulate other types of sleep-like behaviors in C. elegans, as a gene that plays the most significant role in satiety quiescence. A mutation in flp-11 significantly reduces quiescence, whereas over-expression of the gene enhances it. A genetic analysis shows that FLP-11 acts upstream of the cGMP signaling but downstream of the TGFβ pathway, suggesting that TGFβ released from a pair of head sensory neurons (ASI) activates FLP-11 in an interneuron (RIS). Then, cGMP signaling acting in downstream of RIS neurons induces satiety quiescence. Among the 28 INSs genes screened, ins-1, known to play a significant role in starvation-associated behavior working in AIA is inhibitory to satiety quiescence. Our study suggests that specific combinations of neuropeptides are released, and their signals are integrated in order for an animal to gauge its metabolic state and to control satiety quiescence, a feeding-induced sleep-like state in C. elegans.

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Isolation and characterization of extracellular vesicles from Caenorhabditis elegans for multi-omic analysis

10.1101/476226 ◽

2018 ◽

Cited By ~ 4

Author(s):

Joshua C. Russell ◽

Gennifer E. Merrihew ◽

Julia E. Robbins ◽

Nadia Postupna ◽

Tyek-Kyun Kim ◽

...

Keyword(s):

Cell Culture ◽

Caenorhabditis Elegans ◽

Extracellular Vesicles ◽

Mammalian Cell Culture ◽

Model Systems ◽

C Elegans ◽

Isolation And Characterization ◽

Transmission Electron ◽

Invertebrate Model

AbstractCells from bacteria to human release vesicles into their extracellular environment. These extracellular vesicles (EVs) contain multiple classesof molecules, including nucleic acids, proteins, and lipids. The isolation and analysis of EV cargos from mammalian cell culture and liquid biopsysamples has become a powerful approach for uncovering the messages that are packaged into these organelles. However, this approach has not been tenable in invertebrate model systems due to lack of sufficient amounts of pure EVs. Here we report a robust and reproducible procedure to isolateEVs from Caenorhabditis elegans with yields similar to those obtained from human cell culture. Through nanoparticle tracking, transmission electron microscopy, flow cytometry, mass spectrometry, RNAseq, and immunoaffinity analysis we provide the first ever detailed characterization of C. elegans EV composition and demonstrate that C. elegans EVs share fundamentally similar properties with their mammalian counterparts. These include vesicle size, enrichment for lipid rafts, and similar types of RNA and protein cargos. This ability of isolate pure EVs on ascale amenable to multiple types of downstream analyses permits, multi-omics characterization of EV cargos in an invertebrate model system.

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