scholarly journals Cellular Expression and Functional Roles of All 26 Neurotransmitter GPCRs in the C. elegans Egg-Laying Circuit

2020 ◽  
Vol 40 (39) ◽  
pp. 7475-7488
Author(s):  
Robert W. Fernandez ◽  
Kimberly Wei ◽  
Erin Y. Wang ◽  
Deimante Mikalauskaite ◽  
Andrew Olson ◽  
...  
Author(s):  
Robert W. Fernandez ◽  
Kimberly Wei ◽  
Erin Y. Wang ◽  
Deimante Mikalauskaite ◽  
Andrew Olson ◽  
...  

SummaryMaps of the synapses made and neurotransmitters released by all neurons in model systems such as C. elegans have left still unresolved how neural circuits integrate and respond to neurotransmitter signals. Using the egg-laying circuit of C. elegans as a model, we mapped which cells express each of the 26 neurotransmitter G protein coupled receptors (GPCRs) of this organism and also genetically analyzed the functions of all 26 GPCRs. We found that individual neurons express many distinct receptors, epithelial cells often express neurotransmitter receptors, and receptors are often positioned to receive extrasynaptic signals. The egg-laying circuit appears to use redundancy and compensation to achieve functional robustness, as receptor knockouts reveal few defects; however, increasing receptor signaling through overexpression more efficiently reveals receptor functions. This map of neurotransmitter GPCR expression and function in the egg-laying circuit provides a model for understanding GPCR signaling in other neural circuits.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Hayao Ohno ◽  
Morikatsu Yoshida ◽  
Takahiro Sato ◽  
Johji Kato ◽  
Mikiya Miyazato ◽  
...  

Peptide signaling controls many processes involving coordinated actions of multiple organs, such as hormone-mediated appetite regulation. However, the extent to which the mode of action of peptide signaling is conserved in different animals is largely unknown, because many peptides and receptors remain orphan and many undiscovered peptides still exist. Here, we identify two novel Caenorhabditis elegans neuropeptides, LURY-1-1 and LURY-1-2, as endogenous ligands for the neuropeptide receptor-22 (NPR-22). Both peptides derive from the same precursor that is orthologous to invertebrate luqin/arginine-tyrosine-NH2 (RYamide) proneuropeptides. LURY-1 peptides are secreted from two classes of pharyngeal neurons and control food-related processes: feeding, lifespan, egg-laying, and locomotory behavior. We propose that LURY-1 peptides transmit food signals to NPR-22 expressed in feeding pacemaker neurons and a serotonergic neuron. Our results identified a critical role for luqin-like RYamides in feeding-related processes and suggested that peptide-mediated negative feedback is important for satiety regulation in C. elegans.


2018 ◽  
Author(s):  
Kristin Verena Kaltdorf ◽  
Maria Theiss ◽  
Sebastian Matthias Markert ◽  
Mei Zhen ◽  
Thomas Dandekar ◽  
...  

1.AbstractSynaptic vesicles (SVs) are a key component of neuronal signaling and fulfil different roles depending on their composition. In electron micrograms of neurites, two types of vesicles can be distinguished by morphological criteria, the classical “clear core” vesicles (CCV) and the typically larger “dense core” vesicles (DCV), with differences in electron density due to their diverse cargos. Compared to CCVs, the precise function of DCVs is less defined. DCVs are known to store neuropeptides, which function as neuronal messengers and modulators [1]. In C. elegans, they play a role in locomotion, dauer formation, egg-laying, and mechano- and chemosensation [2]. Another type of DCVs, also referred to as granulated vesicles, are known to transport Bassoon, Piccolo and further constituents of the presynaptic density in the center of the active zone (AZ), and therefore are important for synaptogenesis [3].To better understand the role of different types of SVs, we present here a new automated approach to classify vesicles. We combine machine learning with an extension of our previously developed vesicle segmentation workflow, the ImageJ macro 3D ART VeSElecT. With that we reliably distinguish CCVs and DCVs in electron tomograms of C. elegans NMJs using image-based features. Analysis of the underlying ground truth data shows an increased fraction of DCVs as well as a higher mean distance between DCVs and AZs in dauer larvae compared to young adult hermaphrodites. Our machine learning based tools are adaptable and can be applied to study properties of different synaptic vesicle pools in electron tomograms of diverse model organisms.2.Author summaryVesicles are important components of the cell, and synaptic vesicles are central for neuronal signaling. Two types of synaptic vesicles can be distinguished by electron microscopy: the classical “clear core” vesicles (CCVs) and the typically larger “dense core” vesicles (DCVs). The distinct appearance of vesicles is caused by their different cargos. To rapidly distinguish between both vesicle types, we present here a new automated approach to classify vesicles in electron tomograms. We combine machine learning with an extension of our previously developed vesicle segmentation workflow, an ImageJ macro, to reliably distinguish CCVs and DCVs using specific image-based features. The approach was trained and validated using data-sets that were hand curated by microscopy experts. Our technique can be transferred to more extensive comparisons in both stages as well as to other neurobiology questions regarding synaptic vesicles.


2004 ◽  
Vol 9 (2) ◽  
pp. 147-152 ◽  
Author(s):  
Brenda R. Ellerbrock ◽  
Eileen M. Coscarelli ◽  
Mark E. Gurney ◽  
Timothy G. Geary

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)


2002 ◽  
Vol 115 (14) ◽  
pp. 2881-2891
Author(s):  
Monika A. Jedrusik ◽  
Stefan Vogt ◽  
Peter Claus ◽  
Ekkehard Schulze

The histone H1 complement of Caenorhabditis elegans contains a single unusual protein, H1.X. Although H1.X possesses the globular domain and the canonical three-domain structure of linker histones, the amino acid composition of H1.X is distinctly different from conventional linker histones in both terminal domains. We have characterized H1.X in C. elegans by antibody labeling, green fluorescent protein fusion protein expression and RNA interference. Unlike normal linker histones, H1.X is a cytoplasmic as well as a nuclear protein and is not associated with chromosomes. H1.X is most prominently expressed in the marginal cells of the pharynx and is associated with a peculiar cytoplasmic cytoskeletal structure therein, the tonofilaments. Additionally H1.X::GFP is expressed in the cytoplasm of body and vulva muscle cells, neurons, excretory cells and in the nucleoli of embryonic blastomeres and adult gut cells. RNA interference with H1.X results in uncoordinated and egg laying defective animals, as well as in a longitudinally enlarged pharynx. These phenotypes indicate a cytoplasmic role of H1.X in muscle growth and muscle function.


Development ◽  
1991 ◽  
Vol 113 (3) ◽  
pp. 797-803 ◽  
Author(s):  
M.J. Stern ◽  
H.R. Horvitz

In wild-type Caenorhabditis elegans hermaphrodites, two bilaterally symmetric sex myoblasts (SMs) migrate anteriorly to flank the precise center of the gonad, where they divide to generate the muscles required for egg laying (J. E. Sulston and H. R. Horvitz (1977) Devl Biol. 56, 110–156). Although this migration is largely independent of the gonad, a signal from the gonad attracts the SMs to their precise final positions (J. H. Thomas, M. J. Stern and H. R. Horvitz (1990) Cell 62, 1041–1052). Here we show that mutations in either of two genes, egl-15 and egl-17, cause the premature termination of the migrations of the SMs. This incomplete migration is caused by the repulsion of the SMs by the same cells in the somatic gonad that are the source of the attractive signal in wild-type animals.


Development ◽  
2001 ◽  
Vol 128 (18) ◽  
pp. 3395-3404
Author(s):  
Benno Jungblut ◽  
André Pires-daSilva ◽  
Ralf J. Sommer

The invariant cell lineage of nematodes allows the formation of organ systems, like the egg-laying system, to be studied at a single cell level. The Caenorhabditis elegans egg-laying system is made up of the vulva, the mesodermal gonad and muscles and several neurons. The gonad plays a central role in patterning the underlying ectoderm to form the vulva and guiding the migration of the sex myoblasts to their final position. In Pristionchus pacificus, the egg-laying system is homologous to C. elegans, but comparative studies revealed several differences at the cellular and molecular levels during vulval formation. For example, the mesoblast M participates in lateral inhibition, a process that influences the fate of two vulval precursor cells. Here, we describe the M lineage in Pristionchus and show that both the dorsal and ventral M sublineages are involved in lateral inhibition. Mutations in the homeotic gene Ppa-mab-5 cause severe misspecification of the M lineage, resembling more the C. elegans Twist than the mab-5 phenotype. Ectopic differentiation of P8.p in Ppa-mab-5 results from at least two separate interactions between M and P8.p. Thus, interactions among the Pristionchus egg-laying system are complex, involving multiple cells of different tissues occurring over a distance.


Neuron ◽  
1990 ◽  
Vol 4 (5) ◽  
pp. 681-695 ◽  
Author(s):  
C. Li ◽  
Martin Chalfie
Keyword(s):  

Neuron ◽  
2018 ◽  
Vol 97 (3) ◽  
pp. 571-585.e5 ◽  
Author(s):  
Xiaomin Yue ◽  
Jian Zhao ◽  
Xiao Li ◽  
Yuedan Fan ◽  
Duo Duan ◽  
...  

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