scholarly journals Predicting the Function and Subcellular Location of Caenorhabditis elegans Proteins Similar to Saccharomyces cerevisiae β-Oxidation Enzymes

Yeast ◽  
2000 ◽  
Vol 1 (3) ◽  
pp. 188-200
Author(s):  
Aner Gurvitz ◽  
Sigrid Langer ◽  
Martin Piskacek ◽  
Barbara Hamilton ◽  
Helmut Ruis ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Zellweger Syndrome ◽  
Model Organism ◽  
Subcellular Location ◽  
Peroxisomal Disorders ◽  
C Elegans ◽  
Peroxisomal Targeting ◽  
Signal Type ◽  
Targeting Signal

The role of peroxisomal processes in the maintenance of neurons has not been thoroughly investigated. We propose using Caenorhabditis elegans as a model organism for studying the molecular basis underlying neurodegeneration in certain human peroxisomal disorders, e.g. Zellweger syndrome, since the nematode neural network is well characterized and relatively simple in function. Here we have identified C. elegans PEX-5 (C34C6.6) representing the receptor for peroxisomal targeting signal type 1 (PTS1), defective in patients with such disorders. PEX-5 interacted strongly in a two-hybrid assay with Gal4p–SKL, and a screen using PEX-5 identified interaction partners that were predominantly terminated with PTS1 or its variants. A list of C. elegans proteins with similarities to well-characterized yeast β-oxidation enzymes was compiled by homology probing. The possible subcellular localization of these orthologues was predicted using an algorithm based on trafficking signals. Examining the C termini of selected nematode proteins for PTS1 function substantiated predictions made regarding the proteins' peroxisomal location. It is concluded that the eukaryotic PEX5-dependent route for importing PTS1-containing proteins into peroxisomes is conserved in nematodes. C. elegans might emerge as an attractive model system for studying the importance of peroxisomes and affiliated processes in neurodegeneration, and also for studying a β-oxidation process that is potentially compartmentalized in both mitochondria and peroxisomes.

scholarly journals Predicting the Function and Subcellular Location ofCaenorhabditis elegansProteins Similar toSaccharomyces cerevisiaeβ-Oxidation Enzymes

Yeast ◽  
2000 ◽  
Vol 1 (3) ◽  
pp. 188-200 ◽  
Author(s):  
Aner Gurvitz ◽  
Sigrid Langer ◽  
Martin Piskacek ◽  
Barbara Hamilton ◽  
Helmut Ruis ◽  
...  
Keyword(s):  
Zellweger Syndrome ◽  
Model Organism ◽  
Subcellular Location ◽  
Peroxisomal Disorders ◽  
C Elegans ◽  
Peroxisomal Targeting ◽  
Signal Type ◽  
Targeting Signal

The role of peroxisomal processes in the maintenance of neurons has not been thoroughly investigated. We propose usingCaenorhabditis elegansas a model organism for studying the molecular basis underlying neurodegeneration in certain human peroxisomal disorders, e.g. Zellweger syndrome, since the nematode neural network is well characterized and relatively simple in function. Here we have identifiedC. elegansPEX-5 (C34C6.6) representing the receptor for peroxisomal targeting signal type 1 (PTS1), defective in patients with such disorders. PEX-5 interacted strongly in a two-hybrid assay with Gal4p–SKL, and a screen using PEX-5 identified interaction partners that were predominantly terminated with PTS1 or its variants. A list ofC. elegansproteins with similarities to well-characterized yeast β-oxidation enzymes was compiled by homology probing. The possible subcellular localization of these orthologues was predicted using an algorithm based on trafficking signals. Examining the C termini of selected nematode proteins for PTS1 function substantiated predictions made regarding the proteins' peroxisomal location. It is concluded that the eukaryotic PEX5-dependent route for importing PTS1-containing proteins into peroxisomes is conserved in nematodes.C. elegansmight emerge as an attractive model system for studying the importance of peroxisomes and affiliated processes in neurodegeneration, and also for studying a β-oxidation process that is potentially compartmentalized in both mitochondria and peroxisomes.

scholarly journals Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders.

1995 ◽  
Vol 130 (1) ◽  
pp. 51-65 ◽  
Author(s):  
E A Wiemer ◽  
W M Nuttley ◽  
B L Bertolaet ◽  
X Li ◽  
U Francke ◽  
...  
Keyword(s):  
Protein Import ◽  
Zellweger Syndrome ◽  
Complementation Group ◽  
Cell System ◽  
Peroxisomal Disorders ◽  
Peroxisomal Membrane ◽  
Peroxisomal Protein ◽  
Peroxisomal Targeting ◽  
Targeting Signal

Two peroxisomal targeting signals, PTS1 and PTS2, are involved in the import of proteins into the peroxisome matrix. Human patients with fatal generalized peroxisomal deficiency disorders fall into at least nine genetic complementation groups. Cells from many of these patients are deficient in the import of PTS1-containing proteins, but the causes of the protein-import defect in these patients are unknown. We have cloned and sequenced the human cDNA homologue (PTS1R) of the Pichia pastoris PAS8 gene, the PTS1 receptor (McCollum, D., E. Monosov, and S. Subramani. 1993. J. Cell Biol. 121:761-774). The PTS1R mRNA is expressed in all human tissues examined. Antibodies to the human PTS1R recognize this protein in human, monkey, rat, and hamster cells. The protein is localized mainly in the cytosol but is also found to be associated with peroxisomes. Part of the peroxisomal PTS1R protein is tightly bound to the peroxisomal membrane. Antibodies to PTS1R inhibit peroxisomal protein-import of PTS1-containing proteins in a permeabilized CHO cell system. In vitro-translated PTS1R protein specifically binds a serine-lysine-leucine-peptide. A PAS8-PTS1R fusion protein complements the P. pastoris pas8 mutant. The PTS1R cDNA also complements the PTS1 protein-import defect in skin fibroblasts from patients--belonging to complementation group two--diagnosed as having neonatal adrenoleukodystrophy or Zellweger syndrome. The PTS1R gene has been localized to a chromosomal location where no other peroxisomal disorder genes are known to map. Our findings represent the only case in which the molecular basis of the protein-import deficiency in human peroxisomal disorders is understood.

Components Involved in Peroxisome Import, Biogenesis, Proliferation, Turnover, and Movement

1998 ◽  
Vol 78 (1) ◽  
pp. 171-188 ◽  
Author(s):  
SURESH SUBRAMANI
Keyword(s):  
Protein Import ◽  
Protein Translocation ◽  
Peroxisomal Disorders ◽  
Peroxisomal Membrane ◽  
Peroxisomal Protein ◽  
Peroxisomal Targeting ◽  
Docking Proteins ◽  
Targeting Signal ◽  
Peroxisomal Targeting Signal

Subramani, Suresh. Components Involved in Peroxisome Import, Biogenesis, Proliferation, Turnover, and Movement. Physiol. Rev. 78: 171–188, 1998. — In the decade that has elapsed since the discovery of the first peroxisomal targeting signal (PTS), considerable information has been obtained regarding the mechanism of protein import into peroxisomes. The PTSs responsible for the import of matrix and membrane proteins to peroxisomes, the receptors for several of these PTSs, and docking proteins for the PTS1 and PTS2 receptors are known. Many peroxins involved in peroxisomal protein import and biogenesis have been characterized genetically and biochemically. These studies have revealed important new insights regarding the mechanism of protein translocation across the peroxisomal membrane, the conservation of PEX genes through evolution, the role of peroxins in fatal human peroxisomal disorders, and the biogenesis of the organelle. It is clear that peroxisomal protein import and biogenesis have many features unique to this organelle alone. More recent studies on peroxisome degradation, division, and movement highlight newer aspects of the biology of this organelle that promise to be just as exciting and interesting as import and biogenesis.

scholarly journals From the research laboratory to the database: the Caenorhabditis elegans kinome in UniProtKB

2017 ◽  
Vol 474 (4) ◽  
pp. 493-515 ◽  
Author(s):  
Rossana Zaru ◽  
Michele Magrane ◽  
Claire O'Donovan ◽  
Keyword(s):  
Caenorhabditis Elegans ◽  
Model Organism ◽  
Biological Data ◽  
Biological Processes ◽  
Protein Families ◽  
C Elegans ◽  
Cellular Processes ◽  
Primary Literature ◽  
Data Collections

Protein kinases form one of the largest protein families and are found in all species, from viruses to humans. They catalyze the reversible phosphorylation of proteins, often modifying their activity and localization. They are implicated in virtually all cellular processes and are one of the most intensively studied protein families. In recent years, they have become key therapeutic targets in drug development as natural mutations affecting kinase genes are the cause of many diseases. The vast amount of data contained in the primary literature and across a variety of biological data collections highlights the need for a repository where this information is stored in a concise and easily accessible manner. The UniProt Knowledgebase meets this need by providing the scientific community with a comprehensive, high-quality and freely accessible resource of protein sequence and functional information. Here, we describe the expert curation process for kinases, focusing on the Caenorhabditis elegans kinome. The C. elegans kinome is composed of 438 kinases and almost half of them have been functionally characterized, highlighting that C. elegans is a valuable and versatile model organism to understand the role of kinases in biological processes.

scholarly journals The Role of Ca2+ Signaling in Aging and Neurodegeneration: Insights from Caenorhabditis elegans Models

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 204 ◽  
Author(s):  
Javier Alvarez ◽  
Pilar Alvarez-Illera ◽  
Paloma García-Casas ◽  
Rosalba I. Fonteriz ◽  
Mayte Montero
Keyword(s):  
Caenorhabditis Elegans ◽  
Model Organism ◽  
Ample Evidence ◽  
C Elegans ◽  
Physiological Processes ◽  
Human Proteins ◽  
Β Amyloid ◽  
Key Events

Ca2+ is a ubiquitous second messenger that plays an essential role in physiological processes such as muscle contraction, neuronal secretion, and cell proliferation or differentiation. There is ample evidence that the dysregulation of Ca2+ signaling is one of the key events in the development of neurodegenerative processes, an idea called the “calcium hypothesis” of neurodegeneration. Caenorhabditis elegans (C. elegans) is a very good model for the study of aging and neurodegeneration. In fact, many of the signaling pathways involved in longevity were first discovered in this nematode, and many models of neurodegenerative diseases have also been developed therein, either through mutations in the worm genome or by expressing human proteins involved in neurodegeneration (β-amyloid, α-synuclein, polyglutamine, or others) in defined worm tissues. The worm is completely transparent throughout its whole life, which makes it possible to carry out Ca2+ dynamics studies in vivo at any time, by expressing Ca2+ fluorescent probes in defined worm tissues, and even in specific organelles such as mitochondria. This review will summarize the evidence obtained using this model organism to understand the role of Ca2+ signaling in aging and neurodegeneration.

scholarly journals Role of insulin/insulin-like growth factor-1 signaling pathway genes on the lifespan of Caenorhabditis elegans

2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Siti Bazilah Zulkefli ◽  
Ahmad Nazrun Shuid ◽  
Goon Jo Aan
Keyword(s):  
Caenorhabditis Elegans ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Model Organism ◽  
Insulin Like Growth Factor ◽  
C Elegans ◽  
Expression Of Genes ◽  
Differential Expression Of Genes

Aging process is influenced by the insulin/insulin-like growth factor-1 signaling (IIS) pathway or IGF-1 signaling pathway. Studies done on the genes of this pathway were found to affect longevity. However, no conclusive results have been drawn.The purpose of this systematic review is to summarize the function of genes involved in the IIS pathway of Caenorhabditis Elegans (C. elegans), a nematode commonly used as a model organism in molecular genetics and developmental biology. A literature search for relevant studies was done through PubMed and Scopus databases using MeSH keywords Caenorhabditis elegans, C. elegans, nematode, genes, RNA, DNA, IIS pathway, IGF pathway, lifespan, and longevity. The search was limited to studies that were published in the last ten years (2008-May 2018). After exclusion of duplicates, review papers, human, in vitro, and other organismal studies, a total of 76 research articles were selected for further assessments. Data relevant to the effects of IIS genes on the lifespan ofC. eleganswas independently extracted. Reduction of daf-2 and age-1 and overexpression of sir-2.1 were reported to promote increment of the lifespan of C. elegans.  Furthermore, differentially expressed genes that were involved in the protection against oxidative stress, pathogen attack, and toxicity includeins-18, numr-1/-2, sgk-1, and rgs-1. The knockdown of daf-2, age-1, and overexpression of sir-2.1 genes prolonged the lifespan of C. elegans while knockdown of daf-16, hsf-1, sir-2.1 as well as skn-1 shorten the lifespan of C. elegans.In conclusion, the differential expression of genes in the IIS pathway prolongs the lifespan of C. elegans.

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.

Behavioral Effects of Volatile Anesthetics in Caenorhabditis elegans

1996 ◽  
Vol 85 (4) ◽  
pp. 901-912 ◽  
Author(s):  
Michael C. Crowder ◽  
Laynie D. Shebester ◽  
Tim Schedl
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Time Course ◽  
Model Organism ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Effective Concentration ◽  
Forward Genetics ◽  
C Elegans ◽  
Median Effective Concentration

Background The nematode Caenorhabditis elegans offers many advantages as a model organism for studying volatile anesthetic actions. It has a simple, well-understood nervous system; it allows the researcher to do forward genetics; and its genome will soon be completely sequenced. C. elegans is immobilized by volatile anesthetics only at high concentrations and with an unusually slow time course. Here other behavioral dysfunctions are considered as anesthetic endpoints in C. elegans. Methods The potency of halothane for disrupting eight different behaviors was determined by logistic regression of concentration and response data. Other volatile anesthetics were also tested for some behaviors. Established protocols were used for behavioral endpoints that, except for pharyngeal pumping, were set as complete disruption of the behavior. Time courses were measured for rapid behaviors. Recovery from exposure to 1 or 4 vol% halothane was determined for mating, chemotaxis, and gross movement. All experiments were performed at 20 to 22 degrees C. Results The median effective concentration values for halothane inhibition of mating (0.30 vol%-0.21 mM), chemotaxis (0.34 vol%-0.24 mM), and coordinated movement (0.32 vol% - 0.23 mM) were similar to the human minimum alveolar concentration (MAC; 0.21 mM). In contrast, halothane produced immobility with a median effective concentration of 3.65 vol% (2.6 mM). Other behaviors had intermediate sensitivities. Halothane's effects reached steady-state in 10 min for all behaviors tested except immobility, which required 2 h. Recovery was complete after exposure to 1 vol% halothane but was significantly reduced after exposure to immobilizing concentrations. Conclusions Volatile anesthetics selectively disrupt C. elegans behavior. The potency, time course, and recovery characteristics of halothane's effects on three behaviors are similar to its anesthetic properties in vertebrates. The affected nervous system molecules may express structural motifs similar to those on vertebrate anesthetic targets.

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.

Metabolic control of peroxisome abundance

1999 ◽  
Vol 112 (10) ◽  
pp. 1579-1590 ◽  
Author(s):  
C.C. Chang ◽  
S. South ◽  
D. Warren ◽  
J. Jones ◽  
A.B. Moser ◽  
...  
Keyword(s):  
Metabolic Control ◽  
Matrix Protein ◽  
Protein Import ◽  
Zellweger Syndrome ◽  
Mutant Gene ◽  
Peroxisomal Membrane ◽  
Peroxisomal Targeting ◽  
Targeting Signal ◽  
Complementation Groups ◽  
Peroxisomal Targeting Signal

Zellweger syndrome and related disorders represent a group of lethal, genetically heterogeneous diseases. These peroxisome biogenesis disorders (PBDs) are characterized by defective peroxisomal matrix protein import and comprise at least 10 complementation groups. The genes defective in seven of these groups and more than 90% of PBD patients are now known. Here we examine the distribution of peroxisomal membrane proteins in fibroblasts from PBD patients representing the seven complementation groups for which the mutant gene is known. Peroxisomes were detected in all PBD cells, indicating that the ability to form a minimal peroxisomal structure is not blocked in these mutants. We also observed that peroxisome abundance was reduced fivefold in PBD cells that are defective in the PEX1, PEX5, PEX12, PEX6, PEX10, and PEX2 genes. These cell lines all display a defect in the import of proteins with the type-1 peroxisomal targeting signal (PTS1). In contrast, peroxisome abundance was unaffected in cells that are mutated in PEX7 and are defective only in the import of proteins with the type-2 peroxisomal targeting signal. Interestingly, a fivefold reduction in peroxisome abundance was also observed for cells lacking either of two PTS1-targeted peroxisomal beta-oxidation enzymes, acyl-CoA oxidase and 2-enoyl-CoA hydratase/D-3-hydroxyacyl-CoA dehydrogenase. These results indicate that reduced peroxisome abundance in PBD cells may be caused by their inability to import these PTS1-containing enzymes. Furthermore, the fact that peroxisome abundance is influenced by peroxisomal 105-oxidation activities suggests that there may be metabolic control of peroxisome abundance.

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