scholarly journals Identification of novel synaptonemal complex components in C. elegans

2020 ◽  
Vol 219 (5) ◽  
Author(s):  
Matthew E. Hurlock ◽  
Ivana Čavka ◽  
Lisa E. Kursel ◽  
Jocelyn Haversat ◽  
Matthew Wooten ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Structure Function ◽  
Synaptonemal Complex ◽  
Genetic Screens ◽  
Genetic Redundancy ◽  
Homologous Chromosomes ◽  
Superresolution Microscopy ◽  
C Elegans ◽  
Biochemical Identification

The synaptonemal complex (SC) is a tripartite protein scaffold that forms between homologous chromosomes during meiosis. Although the SC is essential for stable homologue pairing and crossover recombination in diverse eukaryotes, it is unknown how individual components assemble into the highly conserved SC structure. Here we report the biochemical identification of two new SC components, SYP-5 and SYP-6, in Caenorhabditis elegans. SYP-5 and SYP-6 are paralogous to each other and play redundant roles in synapsis, providing an explanation for why these genes have evaded previous genetic screens. Superresolution microscopy reveals that they localize between the chromosome axes and span the width of the SC in a head-to-head manner, similar to the orientation of other known transverse filament proteins. Using genetic redundancy and structure–function analyses to truncate C-terminal tails of SYP-5/6, we provide evidence supporting the role of SC in both limiting and promoting crossover formation.

scholarly journals Characterization of Caenorhabditis elegans Homologs of the Down Syndrome Candidate Gene DYRK1A

Genetics ◽  
2003 ◽  
Vol 163 (2) ◽  
pp. 571-580 ◽  
Author(s):  
William B Raich ◽  
Celine Moorman ◽  
Clay O Lacefield ◽  
Jonah Lehrer ◽  
Dusan Bartsch ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Caenorhabditis Elegans ◽  
Trisomy 21 ◽  
Gene Dosage ◽  
Inducible Promoters ◽  
C Elegans ◽  
Dual Specificity ◽  
Specificity Protein

Abstract The pathology of trisomy 21/Down syndrome includes cognitive and memory deficits. Increased expression of the dual-specificity protein kinase DYRK1A kinase (DYRK1A) appears to play a significant role in the neuropathology of Down syndrome. To shed light on the cellular role of DYRK1A and related genes we identified three DYRK/minibrain-like genes in the genome sequence of Caenorhabditis elegans, termed mbk-1, mbk-2, and hpk-1. We found these genes to be widely expressed and to localize to distinct subcellular compartments. We isolated deletion alleles in all three genes and show that loss of mbk-1, the gene most closely related to DYRK1A, causes no obvious defects, while another gene, mbk-2, is essential for viability. The overexpression of DYRK1A in Down syndrome led us to examine the effects of overexpression of its C. elegans ortholog mbk-1. We found that animals containing additional copies of the mbk-1 gene display behavioral defects in chemotaxis toward volatile chemoattractants and that the extent of these defects correlates with mbk-1 gene dosage. Using tissue-specific and inducible promoters, we show that additional copies of mbk-1 can impair olfaction cell-autonomously in mature, fully differentiated neurons and that this impairment is reversible. Our results suggest that increased gene dosage of human DYRK1A in trisomy 21 may disrupt the function of fully differentiated neurons and that this disruption is reversible.

Potential role of protein stabilizers in amelioration of Parkinson's disease and associated effects in transgenic Caenorhabditis elegans model expressing alpha-synuclein

RSC Advances ◽  
2015 ◽  
Vol 5 (95) ◽  
pp. 77706-77715 ◽  
Author(s):  
Supinder Kaur ◽  
Aamir Nazir
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Caenorhabditis Elegans ◽  
Potential Role ◽  
Alpha Synuclein ◽  
C Elegans

Studies employing transgenicC. elegansmodel show that trehalose, a protein stabilizer, alleviates manifestations associated with Parkinson's diseaseviaits inherent activity and through induction of autophagic machinery.

scholarly journals Autophagosomes fuse to phagosomes and play important roles in the degradation of apoptotic cells in Caenorhabditis elegans

2021 ◽  
Author(s):  
Omar Pena-Ramos ◽  
Lucia Chiao ◽  
Xianghua Liu ◽  
Tianyou Yao ◽  
Henry He ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Small Gtpase ◽  
Apoptotic Cells ◽  
Phagosome Maturation ◽  
Double Membrane ◽  
C Elegans ◽  
Intracellular Organelles ◽  
Intracellular Vesicles ◽  
Cellular Components

Autophagosomes are double-membrane intracellular vesicles that degrade protein aggregates, intracellular organelles, and other cellular components. In the nematode Caenorhabditis elegans, 113 somatic cells undergo apoptosis during embryogenesis and are engulfed and degraded by their neighboring cells. We discovered a novel role of autophagosomes in facilitating the degradation of apoptotic cells in C. elegans embryos using a real-time imaging technique. Specifically, double-membrane autophagosomes in engulfing cells are recruited to the surfaces of phagosomes containing apoptotic cells and subsequently fuse to phagosomes, allowing the inner membrane to enter the phagosomal lumen. Mutants defective in the production of autophagosomes display significant delays in the degradation of apoptotic cells, demonstrating the important contribution of autophagosomes to this process. The signaling pathway led by the phagocytic receptor CED-1, CED-1s adaptor CED-6, and the large GTPase dynamin (DYN-1) promote the recruitment of autophagosomes to phagosomes. Moreover, the subsequent fusion of autophagosomes with phagosomes requires the functions of the small GTPase RAB-7 and the HOPS complex. Our findings reveal that, unlike the single-membrane, LC3- associated phagocytosis (LAP) vesicles reported for mammalian phagocytes, canonical autophagosomes function in the clearance of C. elegans apoptotic cells. These findings add autophagosomes to the collection of intracellular organelles that contribute to phagosome maturation, identify novel crosstalk between the autophagy and phagosome maturation pathways, and discover the upstream factors that initiate this crosstalk.

scholarly journals Synaptonemal Complex dimerization regulates chromosome alignment and crossover patterning in meiosis

2020 ◽  
Author(s):  
Spencer G. Gordon ◽  
Lisa E. Kursel ◽  
Kewei Xu ◽  
Ofer Rog
Keyword(s):  
Synaptonemal Complex ◽  
Sequence Homology ◽  
Genetic Information ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Homologous Chromosomes ◽  
C Elegans ◽  
Local Sequence ◽  
Chromosome Alignment ◽  
Dimerization Interface

AbstractDuring sexual reproduction the parental homologous chromosomes find each other (pair) and align along their lengths by integrating local sequence homology with large-scale contiguity, thereby allowing for precise exchange of genetic information. The Synaptonemal Complex (SC) is a conserved zipper-like structure that assembles between the homologous chromosomes. This phase-separated interface brings chromosomes together and regulates exchanges between them. However, the molecular mechanisms by which the SC carries out these functions remain poorly understood. Here we isolated and characterized two mutations in the dimerization interface in the middle of the SC zipper in C. elegans. The mutations perturb both chromosome alignment and the regulation of genetic exchanges. Underlying the chromosome-scale phenotypes are distinct alterations to the way SC subunits interact with one another. We propose that the SC brings homologous chromosomes together through two biophysical activities: obligate dimerization that prevents assembly on unpaired chromosomes; and a tendency to phase-separate that extends pairing interactions along the entire length of the chromosomes.

scholarly journals A Series of Tubes: The C. elegans Excretory Canal Cell as a Model for Tubule Development

2020 ◽  
Vol 8 (3) ◽  
pp. 17 ◽  
Author(s):  
Matthew Buechner ◽  
Zhe Yang ◽  
Hikmat Al-Hashimi
Keyword(s):  
Intracellular Transport ◽  
Renal Tubules ◽  
Genetic Screens ◽  
C Elegans ◽  
Brain Vasculature ◽  
Canal Cell ◽  
Mammalian Tissues ◽  
Cytoskeletal Elements ◽  
Excretory Canal

Formation and regulation of properly sized epithelial tubes is essential for multicellular life. The excretory canal cell of C. elegans provides a powerful model for investigating the integration of the cytoskeleton, intracellular transport, and organismal physiology to regulate the developmental processes of tube extension, lumen formation, and lumen diameter regulation in a narrow single cell. Multiple studies have provided new understanding of actin and intermediate filament cytoskeletal elements, vesicle transport, and the role of vacuolar ATPase in determining tube size. Most of the genes discovered have clear homologues in humans, with implications for understanding these processes in mammalian tissues such as Schwann cells, renal tubules, and brain vasculature. The results of several new genetic screens are described that provide a host of new targets for future studies in this informative structure.

scholarly journals Effects of NAD+ in Caenorhabditis elegans Models of Neuronal Damage

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 993
Author(s):  
Yuri Lee ◽  
Hyeseon Jeong ◽  
Kyung Hwan Park ◽  
Kyung Won Kim
Keyword(s):  
Caenorhabditis Elegans ◽  
Therapeutic Strategy ◽  
Axon Regeneration ◽  
Neuronal Damage ◽  
Biological Processes ◽  
Nematode Caenorhabditis Elegans ◽  
C Elegans ◽  
Neuronal Functions ◽  
Molecular Components

Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor that mediates numerous biological processes in all living cells. Multiple NAD+ biosynthetic enzymes and NAD+-consuming enzymes are involved in neuroprotection and axon regeneration. The nematode Caenorhabditis elegans has served as a model to study the neuronal role of NAD+ because many molecular components regulating NAD+ are highly conserved. This review focuses on recent findings using C. elegans models of neuronal damage pertaining to the neuronal functions of NAD+ and its precursors, including a neuroprotective role against excitotoxicity and axon degeneration as well as an inhibitory role in axon regeneration. The regulation of NAD+ levels could be a promising therapeutic strategy to counter many neurodegenerative diseases, as well as neurotoxin-induced and traumatic neuronal damage.

scholarly journals Aurora-A kinase is required for centrosome maturation in Caenorhabditis elegans

2001 ◽  
Vol 155 (7) ◽  
pp. 1109-1116 ◽  
Author(s):  
Eva Hannak ◽  
Matthew Kirkham ◽  
Anthony A. Hyman ◽  
Karen Oegema
Keyword(s):  
Caenorhabditis Elegans ◽  
Fluorescence Intensity ◽  
Maturation Process ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Wild Type ◽  
C Elegans ◽  
Nuclear Envelope Breakdown ◽  
Pericentriolar Material

Centrosomes mature as cells enter mitosis, accumulating γ-tubulin and other pericentriolar material (PCM) components. This occurs concomitant with an increase in the number of centrosomally organized microtubules (MTs). Here, we use RNA-mediated interference (RNAi) to examine the role of the aurora-A kinase, AIR-1, during centrosome maturation in Caenorhabditis elegans. In air-1(RNAi) embryos, centrosomes separate normally, an event that occurs before maturation in C. elegans. After nuclear envelope breakdown, the separated centrosomes collapse together, and spindle assembly fails. In mitotic air-1(RNAi) embryos, centrosomal α-tubulin fluorescence intensity accumulates to only 40% of wild-type levels, suggesting a defect in the maturation process. Consistent with this hypothesis, we find that AIR-1 is required for the increase in centrosomal γ-tubulin and two other PCM components, ZYG-9 and CeGrip, as embryos enter mitosis. Furthermore, the AIR-1–dependent increase in centrosomal γ-tubulin does not require MTs. These results suggest that aurora-A kinases are required to execute a MT-independent pathway for the recruitment of PCM during centrosome maturation.

scholarly journals Synthesis of paucimannose N-glycans by Caenorhabditis elegans requires prior actions of UDP-N-acetyl-d-glucosamine:alpha-3-d-mannoside beta1,2-N-acetylglucosaminyltransferase I, alpha3,6-mannosidase II and a specific membrane-bound beta-N-acetylglucosaminidase

2003 ◽  
Vol 372 (1) ◽  
pp. 53-64 ◽  
Author(s):  
Wenli ZHANG ◽  
Pinjiang CAO ◽  
Shihao CHEN ◽  
Andrew M. SPENCE ◽  
Shaoxian ZHU ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Metal Ion ◽  
Suitable Model ◽  
Bivalent Metal ◽  
C Elegans ◽  
Membrane Bound ◽  
Specific Membrane ◽  
Optimal Ph ◽  
Nematode Development

We have previously reported three Caenorhabditis elegans genes (gly-12, gly-13 and gly-14) encoding UDP-N-acetyl-d-glucosamine:α-3-d-mannoside β1,2-N-acetylglucosaminyltransferase I (GnT I), an enzyme essential for hybrid and complex N-glycan synthesis. GLY-13 was shown to be the major GnT I in worms and to be the only GnT I cloned to date which can act on [Manα1,6(Manα1,3)Manα1,6](Manα1,3)Manβ1, 4GlcNAcβ1,4GlcNAc-R, but not on Manα1,6(Manα1,3)Manβ1-O-R substrates. We now report the kinetic constants, bivalent-metal-ion requirements, and optimal pH, temperature and Mn2+ concentration for this unusual enzyme. C. elegans glycoproteins are rich in oligomannose (Man6–9GlcNAc2) and ‘paucimannose’ Man3–5GlcNAc2(±Fuc) N-glycans, but contain only small amounts of complex and hybrid N-glycans. We show that the synthesis of paucimannose Man3GlcNAc2 requires the prior actions of GnT I, α3,6-mannosidase II and a membrane-bound β-N-acetylglucosaminidase similar to an enzyme previously reported in insects. The β-N-acetylglucosaminidase removes terminal N-acetyl-d-glucosamine from the GlcNAcβ1, 2Manα1,3Manβ- arm of Manα1,6(GlcNAcβ1,2Manα1,3) Manβ1,4GlcNAcβ1,4GlcNAc-R to produce paucimannose Man3GlcNAc2 N-glycan. N-acetyl-d-glucosamine removal was inhibited by two N-acetylglucosaminidase inhibitors. Terminal GlcNAc was not released from [Manα1,6(Manα1,3)Manα1,6] (GlcNAcβ1,2Manα1,3)Manβ1,4GlcNAcβ1,4GlcNAc-R nor from the GlcNAcβ1,2Manα1,6Manβ- arm. These findings indicate that GLY-13 plays an important role in the synthesis of N-glycans by C. elegans and that therefore the worm should prove to be a suitable model for the study of the role of GnT I in nematode development.

scholarly journals akirin is required for diakinesis bivalent structure and synaptonemal complex disassembly at meiotic prophase I

2013 ◽  
Vol 24 (7) ◽  
pp. 1053-1067 ◽  
Author(s):  
Amy M. Clemons ◽  
Heather M. Brockway ◽  
Yizhi Yin ◽  
Bhavatharini Kasinathan ◽  
Yaron S. Butterfield ◽  
...  
Keyword(s):  
Synaptonemal Complex ◽  
Meiotic Prophase ◽  
Chromosome Condensation ◽  
Late Prophase ◽  
Homologous Chromosomes ◽  
Prophase I ◽  
Meiotic Prophase I ◽  
Evolutionarily Conserved ◽  
Key Events

During meiosis, evolutionarily conserved mechanisms regulate chromosome remodeling, leading to the formation of a tight bivalent structure. This bivalent, a linked pair of homologous chromosomes, is essential for proper chromosome segregation in meiosis. The formation of a tight bivalent involves chromosome condensation and restructuring around the crossover. The synaptonemal complex (SC), which mediates homologous chromosome association before crossover formation, disassembles concurrently with increased condensation during bivalent remodeling. Both chromosome condensation and SC disassembly are likely critical steps in acquiring functional bivalent structure. The mechanisms controlling SC disassembly, however, remain unclear. Here we identify akir-1 as a gene involved in key events of meiotic prophase I in Caenorhabditis elegans. AKIR-1 is a protein conserved among metazoans that lacks any previously known function in meiosis. We show that akir-1 mutants exhibit severe meiotic defects in late prophase I, including improper disassembly of the SC and aberrant chromosome condensation, independently of the condensin complexes. These late-prophase defects then lead to aberrant reconfiguring of the bivalent. The meiotic divisions are delayed in akir-1 mutants and are accompanied by lagging chromosomes. Our analysis therefore provides evidence for an important role of proper SC disassembly in configuring a functional bivalent structure.

scholarly journals A compartmentalized signaling network mediates crossover control in meiosis

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Liangyu Zhang ◽  
Simone Köhler ◽  
Regina Rillo-Bohn ◽  
Abby F Dernburg
Keyword(s):  
Caenorhabditis Elegans ◽  
Symmetry Breaking ◽  
Synaptonemal Complex ◽  
Chromosome Segregation ◽  
Molecular Basis ◽  
Liquid Crystalline ◽  
Ring Finger ◽  
Homologous Chromosomes ◽  
Crossover Interference ◽  
Ring Finger Proteins

During meiosis, each pair of homologous chromosomes typically undergoes at least one crossover (crossover assurance), but these exchanges are strictly limited in number and widely spaced along chromosomes (crossover interference). The molecular basis for this chromosome-wide regulation remains mysterious. A family of meiotic RING finger proteins has been implicated in crossover regulation across eukaryotes. Caenorhabditis elegans expresses four such proteins, of which one (ZHP-3) is known to be required for crossovers. Here we investigate the functions of ZHP-1, ZHP-2, and ZHP-4. We find that all four ZHP proteins, like their homologs in other species, localize to the synaptonemal complex, an unusual, liquid crystalline compartment that assembles between paired homologs. Together they promote accumulation of pro-crossover factors, including ZHP-3 and ZHP-4, at a single recombination intermediate, thereby patterning exchanges along paired chromosomes. These proteins also act at the top of a hierarchical, symmetry-breaking process that enables crossovers to direct accurate chromosome segregation.

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