Distribution and Transport of Cholesterol inCaenorhabditis elegans

Cholesterol transport is an essential process in all multicellular organisms. In this study we applied two recently developed approaches to investigate the distribution and molecular mechanisms of cholesterol transport in Caenorhabditis elegans. The distribution of cholesterol in living worms was studied by imaging its fluorescent analog, dehydroergosterol, which we applied to the animals by feeding. Dehydroergosterol accumulates primarily in the pharynx, nerve ring, excretory gland cell, and gut of L1–L3 larvae. Later, the bulk of dehydroergosterol accumulates in oocytes and spermatozoa. Males display exceptionally strong labeling of spermatids, which suggests a possible role for cholesterol in sperm development. In a complementary approach, we used a photoactivatable cholesterol analog to identify cholesterol-binding proteins in C. elegans. Three major and several minor proteins were found specifically cross-linked to photocholesterol after UV irradiation. The major proteins were identified as vitellogenins. rme-2 mutants, which lack the vitellogenin receptor, fail to accumulate dehydroergosterol in oocytes and embryos and instead accumulate dehydroergosterol in the body cavity along with vitellogenin. Thus, uptake of cholesterol byC. elegans oocytes occurs via an endocytotic pathway involving yolk proteins. The pathway is a likely evolutionary ancestor of mammalian cholesterol transport.

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Screening for Presenilin Inhibitors Using the Free-Living Nematode, Caenorhabditis elegans

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057103261038 ◽

2004 ◽

Vol 9 (2) ◽

pp. 147-152 ◽

Cited By ~ 19

Author(s):

Brenda R. Ellerbrock ◽

Eileen M. Coscarelli ◽

Mark E. Gurney ◽

Timothy G. Geary

Keyword(s):

Caenorhabditis Elegans ◽

High Throughput Screening ◽

Screening Method ◽

Genetic System ◽

Body Cavity ◽

Egg Laying ◽

The Body ◽

Loss Of Function ◽

C Elegans ◽

Automated Method

Caenorhabditis elegans contains 3 homologs of presenilin genes that are associated with Alzheimer s disease. Loss-of-function mutations in C. elegans genes cause a defect in egg laying. In humans, loss of presenilin-1 (PS1) function reduces amyloid-beta peptide processing from the amyloid protein precursor. Worms were screened for compounds that block egg laying, phenocopying presenilin loss of function. To accommodate even relatively high throughput screening, a semi-automated method to quantify egg laying was devised by measuring the chitinase released into the culture medium. Chitinase is released by hatching eggs, but little is shed into the medium from the body cavity of a hermaphrodite with an egg laying deficient ( egl) phenotype. Assay validation involved measuring chitinase release from wild-type C. elegans (N2 strain), sel-12 presenilin loss-of-function mutants, and 2 strains of C. elegans with mutations in the egl-36K+ channel gene. Failure to find specific presenilin inhibitors in this collection likely reflects the small number of compounds tested, rather than a flaw in screening strategy. Absent defined biochemical pathways for presenilin, this screening method, which takes advantage of the genetic system available in C. elegans and its historical use for anthelminthic screening, permits an entry into mechanism-based discovery of drugs for Alzheimer s disease. ( Journal of Biomolecular Screening 2004:147-152)

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Caenorhabditis elegans exhibits positive gravitaxis

BMC Biology ◽

10.1186/s12915-021-01119-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Wei-Long Chen ◽

Hungtang Ko ◽

Han-Sheng Chuang ◽

David M. Raizen ◽

Haim H. Bau

Keyword(s):

Caenorhabditis Elegans ◽

Molecular Mechanisms ◽

Life Forms ◽

The Body ◽

C Elegans ◽

Neural Processes ◽

Sensory Cilia ◽

Touch Response ◽

Vector Direction ◽

Hydrodynamic Effects

Abstract Background Gravity plays an important role in most life forms on Earth. Yet, a complete molecular understanding of sensing and responding to gravity is lacking. While there are anatomical differences among animals, there is a remarkable conservation across phylogeny at the molecular level. Caenorhabditis elegans is suitable for gene discovery approaches that may help identify molecular mechanisms of gravity sensing. It is unknown whether C. elegans can sense the direction of gravity. Results In aqueous solutions, motile C. elegans nematodes align their swimming direction with the gravity vector direction while immobile worms do not. The worms orient downward regardless of whether they are suspended in a solution less dense (downward sedimentation) or denser (upward sedimentation) than themselves. Gravitaxis is minimally affected by the animals’ gait but requires sensory cilia and dopamine neurotransmission, as well as motility; it does not require genes that function in the body touch response. Conclusions Gravitaxis is not mediated by passive forces such as non-uniform mass distribution or hydrodynamic effects. Rather, it is mediated by active neural processes that involve sensory cilia and dopamine. C. elegans provides a genetically tractable system to study molecular and neural mechanisms of gravity sensing.

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Patterning the Axes: A Lesson from the Root

Plants ◽

10.3390/plants8010008 ◽

2018 ◽

Vol 8 (1) ◽

pp. 8 ◽

Cited By ~ 6

Author(s):

Riccardo Di Mambro ◽

Sabrina Sabatini ◽

Raffaele Dello Ioio

Keyword(s):

Molecular Mechanisms ◽

Developmental Stages ◽

The Body ◽

Plant Roots ◽

Root Tip ◽

Central Question ◽

Symmetric Structure ◽

Pass Through ◽

Multicellular Organisms ◽

Radial Axis

How the body plan is established and maintained in multicellular organisms is a central question in developmental biology. Thanks to its simple and symmetric structure, the root represents a powerful tool to study the molecular mechanisms underlying the establishment and maintenance of developmental axes. Plant roots show two main axes along which cells pass through different developmental stages and acquire different fates: the root proximodistal axis spans longitudinally from the hypocotyl junction (proximal) to the root tip (distal), whereas the radial axis spans transversely from the vasculature tissue (centre) to the epidermis (outer). Both axes are generated by stereotypical divisions occurring during embryogenesis and are maintained post-embryonically. Here, we review the latest scientific advances on how the correct formation of root proximodistal and radial axes is achieved.

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Infection of C. elegans by Haptoglossa Species Reveals Shared Features in the Host Response to Oomycete Detection

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.733094 ◽

2021 ◽

Vol 11 ◽

Author(s):

Manish Grover ◽

Michael K. Fasseas ◽

Clara Essmann ◽

Kenneth Liu ◽

Christian Braendle ◽

...

Keyword(s):

Host Response ◽

Pathogen Detection ◽

Natural Infection ◽

Transcriptional Response ◽

Body Cavity ◽

Infection Process ◽

The Body ◽

Host Responses ◽

C Elegans ◽

Eukaryotic Organisms

Oomycetes are a group of eukaryotic organisms that includes many important pathogens of animals and plants. Within this group, the Haptoglossa genus is characterised by the presence of specialised gun cells carrying a harpoon-like infection apparatus. While several Haptoglossa pathogens have been morphologically described, there are currently no host systems developed to study the infection process or host responses in the lab. In this study, we report that Haptoglossa species are potent natural pathogens of Caenorhabditis nematodes. Using electron microscopy, we characterise the infection process in C. elegans and demonstrate that the oomycete causes excessive tissue degradation upon entry in the body cavity, whilst leaving the host cuticle intact. We also report that the host transcriptional response to Haptoglossa infection shares similarities with the response against the oomycete Myzocytiopsis humicola, a key example of which is the induction of chitinase-like (chil) genes in the hypodermis. We demonstrate that this shared feature of the host response can be mounted by pathogen detection without any infection, as previously shown for M. humicola. These results highlight similarities in the nematode immune response to natural infection by phylogenetically distinct oomycetes.

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BMP signaling controls buckling forces to modulate looping morphogenesis of the gut

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1700307114 ◽

2017 ◽

Vol 114 (9) ◽

pp. 2277-2282 ◽

Cited By ~ 37

Author(s):

Nandan L. Nerurkar ◽

L. Mahadevan ◽

Clifford J. Tabin

Keyword(s):

Small Intestine ◽

Molecular Mechanisms ◽

Critical Role ◽

Tissue Level ◽

Body Cavity ◽

Bmp Signaling ◽

The Body ◽

Differential Growth ◽

Bmp Pathway ◽

Dorsal Mesentery

Looping of the initially straight embryonic gut tube is an essential aspect of intestinal morphogenesis, permitting proper placement of the lengthy small intestine within the confines of the body cavity. The formation of intestinal loops is highly stereotyped within a given species and results from differential-growth–driven mechanical buckling of the gut tube as it elongates against the constraint of a thin, elastic membranous tissue, the dorsal mesentery. Although the physics of this process has been studied, the underlying biology has not. Here, we show that BMP signaling plays a critical role in looping morphogenesis of the avian small intestine. We first exploited differences between chicken and zebra finch gut morphology to identify the BMP pathway as a promising candidate to regulate differential growth in the gut. Next, focusing on the developing chick small intestine, we determined that Bmp2 expressed in the dorsal mesentery establishes differential elongation rates between the gut tube and mesentery, thereby regulating the compressive forces that buckle the gut tube into loops. Consequently, the number and tightness of loops in the chick small intestine can be increased or decreased directly by modulation of BMP activity in the small intestine. In addition to providing insight into the molecular mechanisms underlying intestinal development, our findings provide an example of how biochemical signals act on tissue-level mechanics to drive organogenesis, and suggest a possible mechanism by which they can be modulated to achieve distinct morphologies through evolution.

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First identification of a phosphorylcholine-substituted protein from Caenorhabditis elegans: isolation and characterization of the aspartyl protease ASP-6

Biological Chemistry ◽

10.1515/bc.2006.186 ◽

2006 ◽

Vol 387 (10/11) ◽

pp. 1487-1493 ◽

Cited By ~ 6

Author(s):

Günter Lochnit ◽

Julia Grabitzki ◽

Björn Henkel ◽

Nektarios Tavernarakis ◽

Rudolf Geyer

Keyword(s):

Caenorhabditis Elegans ◽

Chimeric Protein ◽

Body Cavity ◽

The Body ◽

Parasitic Nematodes ◽

Aspartyl Protease ◽

Developmental Studies ◽

C Elegans ◽

Isolation And Characterization ◽

Parasitic Worms

AbstractCaenorhabditis elegansis a widely accepted model system for parasitic nematodes, drug screening and developmental studies. Similar to parasitic worms,C. elegansexpresses glycosphingolipids and glycoproteins carrying, in part, phosphorylcholine (PCho) substitutions, which might play important roles in nematode development, fertility and, at least in the case of parasites, survival within the host. With the exception of a major secretory/excretory product fromAcanthocheilonema viteae(ES-62), no protein carrying this epitope has been studied in detail yet. Here we report on the identification, characterization and localization of the aspartyl protease ASP-6 ofC. elegans, which is excreted by the nematode in aPCho-substituted form. Within the worm, most prominent expression of the protein is observed in the intestine, while muscle and epithelial cells expressasp-6to a lesser extent. In animals harboring an ASP-6::GFP fusion protein, diffuse fluorescence throughout the body cavity of adult worms indicates that the chimeric protein is secreted.

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Induction of ASABF (Ascaris suum antibacterial factor)-type antimicrobial peptides by bacterial injection: novel members of ASABF in the nematode Ascaris suum

Biochemical Journal ◽

10.1042/bj20021948 ◽

2003 ◽

Vol 371 (3) ◽

pp. 663-668 ◽

Cited By ~ 21

Author(s):

Ajitha PILLAI ◽

Satoshi UENO ◽

Hong ZHANG ◽

Yusuke KATO

Keyword(s):

Immune Response ◽

Antimicrobial Peptides ◽

Expressed Sequence Tag ◽

Genetic Model ◽

Ascaris Suum ◽

Body Cavity ◽

The Body ◽

C Elegans ◽

Factor Type ◽

Invertebrate Models

Recently, invertebrate models have been widely used for the study of innate immunity. Nematodes are novel potential candidates because of the experimental advantages of Caenorhabditis elegans. However, whether nematodes have active immune responses is still ambiguous. Previously, we reported ASABF (Ascaris suumantibacterial factor)-type antimicrobial peptides in the parasitic nematode Ascaris suum and the genetic model nematode C. elegans. Further screening of a cDNA library and an expressed-sequence-tag database search detected five novel members of ASABF (ASABF-β, -γ, -δ, -ε and -ζ) in A. suum. The transcripts for ASABF-α, -β, -γ, and -δ clearly increased in the body wall, and also in the intestine for ASABF-δ, 4 h after injection of heat-killed bacteria into the pseudocoelom (body cavity), suggesting that these peptides are inducible in the acute phase of immune response. These results also suggest that the nematodes can recognize bacteria in the pseudocoelomic fluid and evoke an active immune response.

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How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

Biochemical Society Transactions ◽

10.1042/bst20190944 ◽

2020 ◽

Vol 48 (3) ◽

pp. 1019-1034 ◽

Cited By ~ 1

Author(s):

Rachel M. Woodhouse ◽

Alyson Ashe

Keyword(s):

Histone Modifications ◽

Molecular Mechanisms ◽

Epigenetic Inheritance ◽

Nematode Caenorhabditis Elegans ◽

Histone Methyltransferases ◽

Transgenerational Epigenetic Inheritance ◽

C Elegans ◽

Recent Developments ◽

Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

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