Drosophila melanogaster cellular repressor of E1A-stimulated genes is a lysosomal protein essential for fly development

Kowalewski-Nimmerfall, Elisabeth; Schähs, Philipp; Maresch, Daniel; Rendić, Dubravko; Krämer, Helmut; Mach, Lukas

doi:10.1016/j.bbamcr.2014.08.012

Cited by 17 publications

(21 citation statements)

References 44 publications

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“…Kowalewski‐Nimmerfall et al. () reported on a Drosophila CREG (dCREG) that localizes to lysosomes. Experiments with gene‐knockout Drosophila lines show ablating the protein is lethal at the late pupal stage, indicating dCREG is essential for development of the fly.…”

Section: Discussionmentioning

confidence: 99%

“…Mammals express a secreted glycoprotein, cellular repressor of E1A-stimulated genes (CREG) that inhibits E1A-stimulated effects (Yang et al, 2011). Kowalewski-Nimmerfall et al (2014) reported on a Drosophila CREG (dCREG) that localizes to lysosomes. Experiments with gene-knockout Drosophila lines show ablating the protein is lethal at the late pupal stage, indicating dCREG is essential for development of the fly.…”

Section: Discussionmentioning

confidence: 99%

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LARVAL X‐RAY IRRADIATION INFLUENCES PROTEIN EXPRESSION IN PUPAE OF THE ORIENTAL FRUIT FLY, BACTROCERA DORSALIS

Chang

Goodman

Ringbauer

et al. 2016

Arch Insect Biochem Physiol

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The sterile insect technique (SIT) was developed to eradicate the new world screwworm from the southern United States and Mexico, and became a component of many area-wide integrated pest management programs, particularly useful in managing tephritid fruit flies. SIT is based on the idea of rearing and sterilizing male pests, originally by ionizing radiation, and then releasing into field, where they compete for and mate with wild females. Mating with sterile males leads to reduced fecundity to lower pest populations. There are concerns with the use and distribution of radioisotopes for SIT programs, which have led to developing X-ray irradiation protocols to sterilize insects. We considered the possibility that X-ray irradiation exerts sublethal impacts aside form sterilizing insects. Such effects may not be directly observable, which led us to the hypothesis that X-ray irradiation in one life stage creates alterations in biological fitness and protein expression in the subsequent stage. We tested our hypothesis by irradiating larvae of Bactrocera dorsalis. There are two major points. One, exposing larvae to X-ray treatments led to reduced adult emergence, fecundity, fertility, and flight capacity from the corresponding pupae and emerged adults. Two, the X-ray treatments led to substantial expression changes in 27 pupal proteins. We assorted the 67 spots representing these proteins into three groups, metabolism, development, and structure. Our interpretation is these X-ray induced changes in biological performance and protein expression indicate their adult counterparts may be disabled in their abilities to successfully compete for and mate wild females in native habitats.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

LARVAL X‐RAY IRRADIATION INFLUENCES PROTEIN EXPRESSION IN PUPAE OF THE ORIENTAL FRUIT FLY, BACTROCERA DORSALIS

Chang

Goodman

Ringbauer

et al. 2016

Arch Insect Biochem Physiol

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“…CREG is reported to predominantly localize within lysosomes [8][9][10]. Therefore, we investigated the effect of CREG on lysosome function in macrophages.…”

Section: Creg Protein Modulates Lysosomal Maturationmentioning

confidence: 98%

“…Recently, CREG is identified to be a bona fide lysosome protein and undergoes proteolytic maturation by lysosomal cysteine proteases in the course of their biosynthesis [8,9]. Expression of CREG is highest in lymph nodes and monocytes in both human and murine tissues as shown in EST databases on the NCBI-UniGene site.…”

Section: Introductionmentioning

confidence: 97%

Cellular repressor of E1A-stimulated genes inhibits inflammation to decrease atherosclerosis in ApoE−/− mice

Sun

Tian

Liu

et al. 2015

Journal of Molecular and Cellular Cardiology

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“…This suggests that the Man 6-P-dependent sorting mechanism is absent in flies. Most recently, Kowalewski-Nimmerfall et al reported that RNAi knockdown of LERP in S2 cells had only a small effect on the retention of the lysosomal enzyme cathepsin L and no effect on lysosomal CREG (cellular repressor of EIA-stimulated genes retention), leading them to suggest that LERP is not a universal sorting receptor for lysosomal proteins in flies ( Kowalewski-Nimmerfall et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

The lysosomal enzyme receptor protein (LERP) is not essential, but is implicated in lysosomal function inDrosophila melanogaster

et al. 2015

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The lysosomal enzyme receptor protein (LERP) of Drosophila melanogaster is the ortholog of the mammalian cation-independent mannose 6-phosphate (Man 6-P) receptor, which mediates trafficking of newly synthesized lysosomal acid hydrolases to lysosomes. However, flies lack the enzymes necessary to make the Man 6-P mark, and the amino acids implicated in Man 6-P binding by the mammalian receptor are not conserved in LERP. Thus, the function of LERP in sorting of lysosomal enzymes to lysosomes in Drosophila is unclear. Here, we analyze the consequence of LERP depletion in S2 cells and intact flies. RNAi-mediated knockdown of LERP in S2 cells had little or no effect on the cellular content or secretion of several lysosomal hydrolases. We generated a novel Lerp null mutation, LerpF6, which abolishes LERP protein expression. Lerp mutants have normal viability and fertility and display no overt phenotypes other than reduced body weight. Lerp mutant flies exhibit a 30–40% decrease in the level of several lysosomal hydrolases, and are hypersensitive to dietary chloroquine and starvation, consistent with impaired lysosome function. Loss of LERP also enhances an eye phenotype associated with defective autophagy. Our findings implicate Lerp in lysosome function and autophagy.

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Drosophila melanogaster cellular repressor of E1A-stimulated genes is a lysosomal protein essential for fly development

Cited by 17 publications

References 44 publications

LARVAL X‐RAY IRRADIATION INFLUENCES PROTEIN EXPRESSION IN PUPAE OF THE ORIENTAL FRUIT FLY, BACTROCERA DORSALIS

LARVAL X‐RAY IRRADIATION INFLUENCES PROTEIN EXPRESSION IN PUPAE OF THE ORIENTAL FRUIT FLY, BACTROCERA DORSALIS

Cellular repressor of E1A-stimulated genes inhibits inflammation to decrease atherosclerosis in ApoE−/− mice

The lysosomal enzyme receptor protein (LERP) is not essential, but is implicated in lysosomal function inDrosophila melanogaster

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