Nucleotide Sequence of a cDNA Clone Encoding aCaenorhabditis elegansHomolog of Mammalian Alkyl-Dihydroxyacetonephosphate Synthase: Evolutionary Switching of Peroxisomal Targeting Signals

Vet, Edwin C.J.M. de; Prinsen, Hubertus C.M.T.; Bosch, H. van den

doi:10.1006/bbrc.1997.7950

Cited by 18 publications

(10 citation statements)

References 20 publications

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“…In C. elegans, ADHAPS is targeted to peroxisomes by a PTS1 (8,39). Our study shows that these proteins are required for the normal development of C. elegans.…”

Section: Peroxisomal Metabolic Functions and Peroxins Influence The Dmentioning

confidence: 69%

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RNA interference of peroxisome-related genes inC. elegans: a new model for human peroxisomal disorders

Petriv

Pilgrim

Rachubinski

et al. 2002

Physiological Genomics

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RNA-mediated interference (RNAi) for the posttranscriptional silencing of genes was used to evaluate the importance of various peroxisomal enzymes and peroxins for the development of Caenorhabditis elegans and to compare the roles of these proteins in the nematode to their roles in yeasts and humans. The nematode counterparts of the human ATP-binding cassette half-transporters, the enzymes alkyldihydroxyacetonephosphate synthase and Δ3,5-Δ 2,4-dienoyl-CoA isomerase, the receptors for peroxisomal membrane and matrix proteins (Pex19p and Pex5p), and components of the docking and translocation machineries for matrix proteins (Pex13p and Pex12p) are essential for the development of C. elegans. Unexpectedly, RNAi silencing of the acyl-CoA synthetase-mediated activation of fatty acids, the α- and β-oxidation of fatty acids, the intraperoxisomal decomposition of hydrogen peroxide, and the peroxins Pex1p, Pex2p, and Pex6p had no apparent effect on C. elegans development. The described analysis of functional gene knockouts through RNAi provides a basis for the use of C. elegans as a valuable model system with which to study the molecular and physiological defects underlying the human peroxisomal disorders.

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“…In C. elegans, ADHAPS is targeted to peroxisomes by a PTS1 (8,39). Our study shows that these proteins are required for the normal development of C. elegans.…”

Section: Peroxisomal Metabolic Functions and Peroxins Influence The Dmentioning

confidence: 69%

“…In humans, defects in ADHAPS result in a peroxisomal single enzyme disorder, RCDP type 3 (9). ADHAPS, which is targeted to peroxisomes by a PTS2 in mammals (7), contains a PTS1 in C. elegans (8). The C. elegans counterpart of human ADHAPS is encoded by ORF Y50D7A.7 (39).…”

Section: In Silico Search For C Elegans Orthologs Of Human Peroxisommentioning

confidence: 99%

RNA interference of peroxisome-related genes inC. elegans: a new model for human peroxisomal disorders

Petriv

Pilgrim

Rachubinski

et al. 2002

Physiological Genomics

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“…The probable counterpart of the mammalian type‐I thiolase responsible for the peroxisomal degradation of straight‐chain fatty acid is a protein encoded by ORF T02G5.8 of C. elegans . This putative protein carries a PTS1‐like sequence (Gln‐Lys‐Leu) instead of PTS2, which the mammalian peroxisomal thiolase has, an evolutionary switching of PTSs between mammals and nematode as reported in alkyl‐dihydroxyacetonephosphate synthase [35]. The intestinal localization of P‐44 is merely a reflection of the simple anatomy of C. elegans; the multifunctional intestinal cells must also serve hepatic functions.…”

Section: Resultsmentioning

confidence: 99%

Type‐II 3‐oxoacyl‐CoA thiolase of the nematode Caenorhabditis elegans is located in peroxisomes, highly expressed during larval stages and induced by clofibrate

Maebuchi

Togo

Yokota³

et al. 1999

European Journal of Biochemistry

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We examined the expression and localization of type-II 3-oxoacyl-CoA thiolase in the nematode Caenorhabditis elegans. Type-II thiolase acts on 3-oxoacyl-CoA esters with a methyl group at the a carbon, whereas conventional thiolases do not. Mammalian type-II thiolase, which is also termed sterol carrier protein x (SCPx) or SCP2/3-oxoacyl-CoA thiolase, is located in the peroxisomes and involved in phytanic acid degradation and most probably in bile acid synthesis. The nematode enzyme lacks the SCP2 domain, which carries the peroxisomal-targeting signal, but produces bile acids in a cell-free system. Northern and Western blot analyses demonstrated that C. elegans expressed type-II thiolase throughout its life cycle, especially during the larval stages, and that the expression was significantly enhanced by the addition of clofibrate at 5 mm or more to the culture medium. Whole-mount in situ hybridization and immunostaining of L4 larvae revealed that the enzyme was mainly expressed in intestinal cells, which are multifunctional like many of the cell types in C. elegans. Subcellular fractionation and indirect immunoelectron microscopy of the nematode detected the enzyme in the matrix of peroxisomes. These results indicate the fundamental homology between mammalian SCPx and the nematode enzyme regardless of whether the SCP2 part is fused, suggesting their common physiological roles.

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“…The human peroxins for which neither C. elegans nor Caenorhabditis briggsae homologs could be identified are PEX7 (the PTS2 receptor) and PEX16, which is a peroxisomal membrane protein required for membrane biogenesis (Eitzen et al, 1995). It is not surprising that we did not identify a PEX-7 homolog, given that C. elegans orthologs of PTS-2-containing proteins have no detectable PTS-2 signal, but instead have acquired a PTS-1 signal (de Vet et al, 1998;Motley et al, 2000). We also searched the entire C. elegans genome for any predicted open reading frames containing a PTS-2 motif and found none.…”

Section: Visualization Of Peroxisomes In C Elegansmentioning

confidence: 85%

Modeling human peroxisome biogenesis disorders in the nematodeCaenorhabditis elegans

Thieringer

Moellers

Dodt

et al. 2003

Journal of Cell Science

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Peroxisomes are ubiquitous eukaryotic organelles. The proteins required for peroxisome biogenesis are called peroxins, and mutations in the peroxin genes cause the devastating human developmental syndromes called the peroxisome biogenesis disorders. Our interest is in elaborating the roles that peroxisomes play in Caenorhabditis elegans development, and in establishing an invertebrate model system for the human peroxisome biogenesis disorders. The genome of C. elegans encodes homologs of 11 of the 13 human peroxins. We disrupted five nematode peroxins using RNA interference(RNAi) and found that RNAi knockdown of each one causes an early larval arrest at the L1 stage. Using a green fluorescent protein reporter targeted to the peroxisome, we establish that peroxisomal import is impaired in prx-5(RNAi) nematodes. prx-5(RNAi) animals are blocked very early in the L1 stage and do not initiate normal postembryonic cell divisions,similar to starvation-arrested larvae. Cell and axonal migrations that normally occur during the L1 stage also appear blocked. We conclude that peroxisome function is required for C. elegans postembryonic development and that disruption of peroxisome assembly by prx-5(RNAi)prevents scheduled postembryonic cell divisions. Defects in the cellular localization of peroxisomal proteins and in development are shared features of human and nematode peroxisome biogenesis disorders. In setting up a C. elegans model of peroxisomal biogenesis disorders, we suggest that genetic screens for suppression of the Prx developmental block will facilitate identification of novel intervention strategies and may provide new insights into human disease pathogenesis.

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Nucleotide Sequence of a cDNA Clone Encoding aCaenorhabditis elegansHomolog of Mammalian Alkyl-Dihydroxyacetonephosphate Synthase: Evolutionary Switching of Peroxisomal Targeting Signals

Cited by 18 publications

References 20 publications

RNA interference of peroxisome-related genes inC. elegans: a new model for human peroxisomal disorders

RNA interference of peroxisome-related genes inC. elegans: a new model for human peroxisomal disorders

Type‐II 3‐oxoacyl‐CoA thiolase of the nematode Caenorhabditis elegans is located in peroxisomes, highly expressed during larval stages and induced by clofibrate

Modeling human peroxisome biogenesis disorders in the nematodeCaenorhabditis elegans

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