The Unique GGA Clathrin Adaptor of Drosophila melanogaster Is Not Essential

Luan, Shan; Ilvarsonn, Anne M.; Eissenberg, Joel C.

doi:10.1371/journal.pone.0045163

Cited by 3 publications

(2 citation statements)

References 54 publications

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“…In Drosophila, null mutations in stonin (Stoned‐B) are embryonic lethal , indicating a non‐redundant function. However, the single GGA gene in flies is dispensable . In yeast, there is some functional redundancy between GGAs and AP‐1: knocking out either one on its own causes at most a mild defect in endosomal sorting, but knocking out both severely compromises cell viability .…”

Section: Additional Adaptorsmentioning

confidence: 99%

Forty Years of Clathrin‐coated Vesicles

Robinson

2015

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The purification of coated vesicles and the discovery of clathrin by Barbara Pearse in 1975 was a landmark in cell biology. Over the past 40 years, work from many labs has uncovered the molecular details of clathrin and its associated proteins, including how they assemble into a coated vesicle and how they select cargo. Unexpected connections have been found with signalling, development, neuronal transmission, infection, immunity and genetic disorders. But there are still a number of unanswered questions, including how clathrin-mediated trafficking is regulated and how the machinery evolved.

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Section: Additional Adaptorsmentioning

confidence: 99%

Forty Years of Clathrin‐coated Vesicles

Robinson

2015

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“…Exposure of Drosophila to 10–20 mM dietary chloroquine, a drug that raises lysosomal pH and impairs lysosome hydrolytic activity, is lethal to wild-type flies over a period of days ( Luan et al, 2012 ). We hypothesized that if loss of LERP impairs lysosomal activity, further impairment due to chloroquine exposure would enhance the lysosomal defect and result in enhanced lethality.…”

Section: Resultsmentioning

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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Differential autophagic cell death under stress with ectopic cytoplasmic and mitochondrial-specific PPP2R2B in human neuroblastoma cells

Fang

Hsieh

et al. 2013

Apoptosis

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Protein phosphatase 2A is one of four major classes of serine/threonine phosphatases. Overexpression of brain-specific regulatory subunit PPP2R2 in neuron cells is implicated in pathogenesis. The alternative splicing of PPP2R2B encodes two isoforms. They are subunit of cytoplasmic specific Bβ1 and mitochondria-targeted Bβ2. The two constructs were transfected into human neuroblastoma cells, SK-N-SH, respectively, and the stable clones overexpressing either Bβ1 or Bβ2 established. We have reported that Bβ2 clones are sensitive to reactive oxygen species (ROS) treatment by inducing autophagic cell death. To study more on the onset of neuropathogenesis under strain, both clones were exposed to different environmental stress, e.g. starvation and endoplasmic reticulum (ER) stress. To learn how PPP2R2B overexpression responds to starvation, cells were incubated in Hank's buffered salt solution of deprived nutrient. Cell death was induced in Bβ1 clones after 6 h starvation, but not in Bβ2 clones. The pharmacological inhibitor, Bafilomycin A1, rescued the cell death while suppressing autophagy. On the other hand, to assess how cells respond to ER stress, the cells were treated with 0.1 μM of N-glycosylation inhibitor, tunicamycin (TM). In contrast with Bβ1, the apoptotic cell death appeared in Bβ2 after 48 h treatment. The formation of autophagolysosome was detected in Bβ2 following 12 h treatment with TM as evidenced by lysotracker and GFP-LC3 staining for fluorescence microscopy analysis. The autophagy inhibitor, 3-methyladenine, salvaged the final apoptosis. The stable cell lines with ectopically transfected PPP2R2B genes encoding isoforms of brain-specific regulatory subunit exhibit distinct apoptosis under different stressors. The induced autophagic apoptotic cell death is related to mitochondrial membrane potential drop and ROS generation. Disturbance of autophagy alleviates the induced cell death. The results promised a good model for understanding the onset in pathogenesis under stress in neuron cells with aberrant PPP2R2B expression.

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The Unique GGA Clathrin Adaptor of Drosophila melanogaster Is Not Essential

Cited by 3 publications

References 54 publications

Forty Years of Clathrin‐coated Vesicles

Forty Years of Clathrin‐coated Vesicles

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

Differential autophagic cell death under stress with ectopic cytoplasmic and mitochondrial-specific PPP2R2B in human neuroblastoma cells

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