A Systematic Cell‐Based Analysis of Localization of Predicted <i>Drosophila</i> Peroxisomal Proteins

Baron, Matthew N.; Klinger, Christen M.; Rachubinski, Richard A.; Simmonds, Andrew

doi:10.1111/tra.12384

Cited by 26 publications

(56 citation statements)

References 61 publications

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“…PEX5 and PEX7 homologues are found across the eukaryota, including kinetoplastids, yeasts, plants and mammals (Kanzawa et al, 2012;Kragler et al, Mutation of Drosophila Pex genes is linked to a range of phenotypes, including lethality (Pex1, Pex3, Pex19) and male sterility (Pex16) (Beard and Holtzman, 1987;Bulow et al, 2018;Chen et al, 2010;Faust et al, 2014;Mast et al, 2011;Nakayama et al, 2011). In Drosophila S2 cells, knock down of Pex5 transcript reduces targeting of PTS1containing proteins to peroxisomes function, while depletion or overexpression of Pex7 transcript led to smaller or larger peroxisomes, respectively, than normal (Baron et al, 2016). However, the actual function of Drosophila Pex7 remains unclear, as no bona fide peroxisomal PTS2-containing protein has been identified in Drosophila; fly homologues of peroxisomal proteins trafficked by the PTS2/PEX7 import pathway, e.g.…”

Section: Introductionmentioning

confidence: 99%

Functional characterization of peroxisome biogenic proteins Pex5 and Pex7 of Drosophila

Cara

Rachubinski

Simmonds

2018

Preprint

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Section: Introductionmentioning

confidence: 99%

Functional characterization of peroxisome biogenic proteins Pex5 and Pex7 of Drosophila

Cara

Rachubinski

Simmonds

2018

Preprint

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“…This may be related to the requirement for peroxisomemediated lipid synthesis in cells of the central nervous system. Baron et al, 2016). Together, these data suggest that D. melanogaster Pex7 function is required for normal development of a specific subset of cells, likely of neuronal lineage.…”

mentioning

confidence: 80%

“…The D. melanogaster genome encodes a putative Pex7 homolog only somewhat characterized. To date, different patterns of co-localization of Pex7/peroxisome have been reported, from 0% to 50% co-localized depending on the reporters used (Faust et al, 2012;Baron et al, 2016). There is a requirement for Pex7 in D. melanogaster lipid processing, as homozygous Pex7 mutant larvae have higher levels of circulating free fatty acids and are larger than their wild-type counterparts.…”

Section: Introductionmentioning

confidence: 99%

“…UAS-Pex1 and UAS-Pex7 transgenic strains, the latter produced de novo for this study, were established by Best Gene Inc., Chino Hills CA, USA (https://www.thebestgene.com) using ΦC31 Integrase-mediated germline integration (Bischof et al, 2007;Bateman et al, 2006). The UAS-Pex7 cassette was inserted as the plasmid pPMW-attB-Pex7, derived from pPMW-attB (Addgene, contributor F Perronet) and pENTR-Pex7 (Baron et al, 2016) using Gateway LR Clonase II (ThermoFisher), then transformed into strain y 1 M{vas-int.Dm}ZH-2A w * ; M{3xP3-RFP.attP'}ZH-51C (BDSC).…”

Section: Introductionmentioning

confidence: 99%

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Drosophila melanogaster Peroxisome Biogenesis Factor 7plays a role in embryonic development

Pridie

2019

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Running title: Drosophila melanogaster Pex7Abstract Peroxisomes are organelles responsible for aspects of lipid metabolism and management of reactive oxygen species. Peroxisome Biogenesis Factor (Peroxin, Pex) genes encode proteins essential to peroxisome biogenesis or function. In yeast and mammals, PEROXIN7 acts as a cytosolic receptor protein that targets a subset of enzymes for peroxisome matrix import.Proteins targeted by PEROXIN7 contain a peroxisome targeting sequence 2 (PTS2) motif. The PTS2 was not found in the D. melanogaster homologs of proteins that are PEROXIN7 targets in yeast or mammals, however comparative genomics suggest a Pex7 homolog is present in the D.melanogaster genome. Herein we report novel, tissue-specific patterns for transcription and translation of Pex7 in the D. melanogaster embryo that appear to be strongest in presumptive neuronal lineages. We also show that targeted somatic Pex7 knockout in neural precursors via targeted somatic CRISPR knockout affected survival of mutant embryos. Pex7 over-expression via Gal4-UAS also reduced adult survival but was not deleterious at the embryo stage. Notably, targeted somatic rescue of Pex7 in the neural precursors of Pex7 homozygous mutants also impaired embryo survival. We conclude that D. melanogaster has tissue-specific developmental requirements of Pex7 expression. This may be related to the requirement for peroxisomemediated lipid synthesis in cells of the central nervous system. Baron et al., 2016). Together, these data suggest that D. melanogaster Pex7 function is required for normal development of a specific subset of cells, likely of neuronal lineage. Materials and Methods Drosophila stocks, embryo collection and viability assays

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“…Historically, genetic screens for biochemical phenotypes have identified genes implicated in peroxisome-biogenesis, pexophagy, and peroxisomal biochemistry (SUBRAMANI 1998;KAO et al 2018). More recently, microscopy-based screens have uncovered genes implicated in peroxisome morphology (BARON et al 2016;YOFE et al 2017). These studies have shown that the pathways that regulate peroxisome dynamics (i.e.…”

Section: Introductionmentioning

confidence: 99%

A genetic screen for genes that impact peroxisomes in Drosophila identifies candidate genes for human disease

Graves

Jangam

Tan

et al. 2019

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Peroxisomes are sub-cellular organelles that are essential for proper function of eukaryotic cells. In addition to being the sites of a variety of oxidative reactions, they are crucial regulators of lipid metabolism. Peroxisome loss or dysfunction leads to multisystem diseases in humans that strongly affects the nervous system. In order to uncover previously unidentified genes and mechanisms that impact peroxisomes, we conducted a genetic screen on a collection of lethal mutations on the X chromosome in Drosophila.Using the number, size and morphology of GFP tagged peroxisomes as a readout, we screened for mutations that altered the number and morphology of peroxisomes based on clonal analysis and confocal microscopy. From this screen, we identified 18 genes that cause increases in peroxisome number or altered morphology when mutated. We examined the human homologs of these genes and found that they are involved in a diverse array of cellular processes. Interestingly, the human homologs from the Xchromosome collection are under selective constraint in human populations and are good candidate genes particularly for dominant genetic disease. This in vivo screening approach for peroxisome defects allows identification of novel genes that impact peroxisomes in vivo in a multicellular organism and is a valuable platform to discover genes potentially involved in dominant disease that could affect peroxisomes.

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A Systematic Cell‐Based Analysis of Localization of Predicted Drosophila Peroxisomal Proteins

Abstract: Peroxisomes are membrane-bound organelles found in almost all This will facilitate use of Drosophila as a genetically tractable, multicellular model system for studying key aspects of human peroxisome disease.

Cited by 26 publications

References 61 publications

Functional characterization of peroxisome biogenic proteins Pex5 and Pex7 of Drosophila

Functional characterization of peroxisome biogenic proteins Pex5 and Pex7 of Drosophila

Drosophila melanogaster Peroxisome Biogenesis Factor 7plays a role in embryonic development

A genetic screen for genes that impact peroxisomes in Drosophila identifies candidate genes for human disease

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