Shanjun Chen - Academia.edu (original) (raw)
Papers by Shanjun Chen
Background: A point mutation in the Drosophila gene technical knockout (tko), encoding mitoriboso... more Background: A point mutation in the Drosophila gene technical knockout (tko), encoding mitoribosomal protein S12, was previously shown to cause a phenotype of respiratory chain deficiency, developmental delay, and neurological abnormalities similar to those presented in many human mitochondrial disorders, as well as defective courtship behavior. Methodology/Principal Findings: Here, we describe a transcriptome-wide analysis of gene expression in tko25t mutant flies that revealed systematic and compensatory changes in the expression of genes connected with metabolism, including up-regulation of lactate dehydrogenase and of many genes involved in the catabolism of fats and proteins, and various anaplerotic pathways. Gut-specific enzymes involved in the primary mobilization of dietary fats and proteins, as well as a number of transport functions, were also strongly up-regulated, consistent with the idea that oxidative phosphorylation OXPHOS dysfunction is perceived physiologically as a...
FEBS Journal, 2007
Seminal fluid elicits a variety of physiological and behavioral changes in insect females. In Dro... more Seminal fluid elicits a variety of physiological and behavioral changes in insect females. In Drosophila melanogaster females, sex peptide (SP) is the major seminal agent eliciting oviposition and reduction of receptivity. But SP also has many other effects; for example, it stimulates food intake, egg production, ovulation, juvenile hormone production and antimicrobial peptide synthesis. Thus, SP very probably has several receptors. To identify putative targets and signaling cascades, we studied the genome-wide regulation of genes by microarray analysis of RNA isolated from females after mating with wild-type males or males lacking SP, respectively. In addition, we studied the effects of SP on the proteome of females. Sex peptide regulates gene activity differentially in the head and in the abdomen. Genes coding for unspecific antimicrobial peptides are specifically transcribed in the abdomen, e.g. the antimicrobial peptide drosocin in epithelial tissues of the female genital tract (oviduct and calyx). Hence, SP elicits a systemic [Peng J, Zipperlen P & Kubli E (2005) Curr Biol15, 1690-1694] and an epithelial immune response. Ectopic expression of SP in the fat body of transgenic virgin females (with subsequent secretion into the hemolymph) does not elicit drosocin synthesis in the genital tract. Thus, the receptors for the stimulation of the systemic and the epithelial responses by SP are compartmentalized. The hydroxyproline (P*) motif of SP, P*TKFP*IP*SP*NP*, is identified as a novel elicitor of the innate immune response. We suggest that SP acts by chemical mimicry of sugar components of the bacterial cell wall. Thus, SP may induce the immune system via pattern recognition receptors.
PLoS ONE, 2010
Background: A point mutation in the Drosophila gene technical knockout (tko), encoding mitoriboso... more Background: A point mutation in the Drosophila gene technical knockout (tko), encoding mitoribosomal protein S12, was previously shown to cause a phenotype of respiratory chain deficiency, developmental delay, and neurological abnormalities similar to those presented in many human mitochondrial disorders, as well as defective courtship behavior. Methodology/Principal Findings: Here, we describe a transcriptome-wide analysis of gene expression in tko 25t mutant flies that revealed systematic and compensatory changes in the expression of genes connected with metabolism, including upregulation of lactate dehydrogenase and of many genes involved in the catabolism of fats and proteins, and various anaplerotic pathways. Gut-specific enzymes involved in the primary mobilization of dietary fats and proteins, as well as a number of transport functions, were also strongly up-regulated, consistent with the idea that oxidative phosphorylation OXPHOS dysfunction is perceived physiologically as a starvation for particular biomolecules. In addition, many stressresponse genes were induced. Other changes may reflect a signature of developmental delay, notably a down-regulation of genes connected with reproduction, including gametogenesis, as well as courtship behavior in males; logically this represents a programmed response to a mitochondrially generated starvation signal. The underlying signalling pathway, if conserved, could influence many physiological processes in response to nutritional stress, although any such pathway involved remains unidentified. Conclusions/Significance: These studies indicate that general and organ-specific metabolism is transformed in response to mitochondrial dysfunction, including digestive and absorptive functions, and give important clues as to how novel therapeutic strategies for mitochondrial disorders might be developed.
Current Biology, 2005
rich male peptides [5-7]. Sex-peptide (SP) and Ovulin are products of the accessory glands, and t... more rich male peptides [5-7]. Sex-peptide (SP) and Ovulin are products of the accessory glands, and the Ductus ejacu-Winterthurerstrasse 190 CH-8057 Zü rich latorius peptide (DUP) is synthesized in the ejaculatory duct. They are transferred together with sperm into the Switzerland female during mating [7]. SP and DUP induce both PMR. Ovulin elicits ovulation and oviposition on the first day after mating, but does not affect receptivity [8]. Mating Summary with wild-type males induces the PMR for about 1 week; however, mating with males that do not transfer sperm Background: In many female insects, peptides transelicits PMR only for one day (long-term and short-term ferred in the seminal fluid induce postmating responses PMR, respectively). (This phenomenon has been de-(PMR), such as a drastic increase of egg laying and scribed as "sperm effect" by Manning, [9, 10].) Males reduction of receptivity (readiness to mate). In Drosophlacking functional SP (SP 0 males) elicit only weak PMR ila melanogaster, sex-peptide (SP) elicits short-and lasting about one day [11, 12]. Hence, in vivo SP is the long-term PMR, but only the latter in the presence of major agent eliciting both the short-and the long-term stored sperm (sperm effect). PMR; Ovulin and DUP play only minor roles during the Results: Here, we elucidate the interaction between SP first day after copulation. Because SP 0 males transfer and sperm by immunofluorescence microscopy. Transand store sperm [12], sperm alone cannot induce the genic males were used to study the effects of SP modifi-PMR, but stored sperm are essential for their persiscation on the PMR of females in vivo. We report that tence [9, 10]. Without sperm transfer, or injection of SP binds to sperm with its N-terminal end. In females, physiological amounts of the peptide, SP elicits only the C-terminal part of SP known to be essential to induce short-term PMR [7, 10, 13]. How do SP and sperm interthe PMR is gradually released from stored sperm by act to support the long-term PMR? A possible mechacleavage at a trypsin cleavage site, thus prolonging the nism could be binding of SP to sperm [14]. Here, we PMR. These findings are confirmed by analyzing the show that SP binds to sperm with the N-terminal end. PMR elicited by males containing transgenes encoding During storage, SP is cleaved off from the tail, and the modified SPs. SP lacking the N-terminal end cannot released C-terminal part elicits the long-term PMR. bind, and SP without the trypsin cleavage site binds permanently to sperm. Conclusion: By binding to sperm tails, SP prolongs the Results PMR. Thus, besides a carrier for genetic information, sperm is also the carrier for SP. Binding to sperm may Sex-Peptide Binds to Sperm Stored protect the peptide from degradation by proteases in in the Genital Tract of the Female the hemolymph and, thus, prolong its half-life. Longer We used immunofluorescence to visualize putative sperm tails may transfer more SP and thus increase the binding of peptides to sperm. Sperm were isolated from reproductive fitness of the male. We suggest that this females at different time intervals after mating and were could explain the excessive length of sperm tails in some then incubated with antibodies specific for SP, DUP, or Drosophila species. Ovulin, respectively (Figure 1). DUP binds only to the head and only in the first few hours (data not shown), whereas Ovulin does not bind to sperm at all (Figure
Genetics, 2012
Phenotypes relevant to oxidative phosphorylation (OXPHOS) in eukaryotes are jointly determined by... more Phenotypes relevant to oxidative phosphorylation (OXPHOS) in eukaryotes are jointly determined by nuclear and mitochondrial DNA (mtDNA). Thus, in humans, the variable clinical presentations of mitochondrial disease patients bearing the same primary mutation, whether in nuclear or mitochondrial DNA, have been attributed to putative genetic determinants carried in the “other” genome, though their identity and the molecular mechanism(s) by which they might act remain elusive. Here we demonstrate cytoplasmic suppression of the mitochondrial disease-like phenotype of the Drosophila melanogaster nuclear mutant tko25t, which includes developmental delay, seizure sensitivity, and defective male courtship. The tko25t strain carries a mutation in a mitoribosomal protein gene, causing OXPHOS deficiency due to defective intramitochondrial protein synthesis. Phenotypic suppression was associated with increased mtDNA copy number and increased mitochondrial biogenesis, as measured by the expressio...
Background: A point mutation in the Drosophila gene technical knockout (tko), encoding mitoriboso... more Background: A point mutation in the Drosophila gene technical knockout (tko), encoding mitoribosomal protein S12, was previously shown to cause a phenotype of respiratory chain deficiency, developmental delay, and neurological abnormalities similar to those presented in many human mitochondrial disorders, as well as defective courtship behavior. Methodology/Principal Findings: Here, we describe a transcriptome-wide analysis of gene expression in tko25t mutant flies that revealed systematic and compensatory changes in the expression of genes connected with metabolism, including up-regulation of lactate dehydrogenase and of many genes involved in the catabolism of fats and proteins, and various anaplerotic pathways. Gut-specific enzymes involved in the primary mobilization of dietary fats and proteins, as well as a number of transport functions, were also strongly up-regulated, consistent with the idea that oxidative phosphorylation OXPHOS dysfunction is perceived physiologically as a...
FEBS Journal, 2007
Seminal fluid elicits a variety of physiological and behavioral changes in insect females. In Dro... more Seminal fluid elicits a variety of physiological and behavioral changes in insect females. In Drosophila melanogaster females, sex peptide (SP) is the major seminal agent eliciting oviposition and reduction of receptivity. But SP also has many other effects; for example, it stimulates food intake, egg production, ovulation, juvenile hormone production and antimicrobial peptide synthesis. Thus, SP very probably has several receptors. To identify putative targets and signaling cascades, we studied the genome-wide regulation of genes by microarray analysis of RNA isolated from females after mating with wild-type males or males lacking SP, respectively. In addition, we studied the effects of SP on the proteome of females. Sex peptide regulates gene activity differentially in the head and in the abdomen. Genes coding for unspecific antimicrobial peptides are specifically transcribed in the abdomen, e.g. the antimicrobial peptide drosocin in epithelial tissues of the female genital tract (oviduct and calyx). Hence, SP elicits a systemic [Peng J, Zipperlen P & Kubli E (2005) Curr Biol15, 1690-1694] and an epithelial immune response. Ectopic expression of SP in the fat body of transgenic virgin females (with subsequent secretion into the hemolymph) does not elicit drosocin synthesis in the genital tract. Thus, the receptors for the stimulation of the systemic and the epithelial responses by SP are compartmentalized. The hydroxyproline (P*) motif of SP, P*TKFP*IP*SP*NP*, is identified as a novel elicitor of the innate immune response. We suggest that SP acts by chemical mimicry of sugar components of the bacterial cell wall. Thus, SP may induce the immune system via pattern recognition receptors.
PLoS ONE, 2010
Background: A point mutation in the Drosophila gene technical knockout (tko), encoding mitoriboso... more Background: A point mutation in the Drosophila gene technical knockout (tko), encoding mitoribosomal protein S12, was previously shown to cause a phenotype of respiratory chain deficiency, developmental delay, and neurological abnormalities similar to those presented in many human mitochondrial disorders, as well as defective courtship behavior. Methodology/Principal Findings: Here, we describe a transcriptome-wide analysis of gene expression in tko 25t mutant flies that revealed systematic and compensatory changes in the expression of genes connected with metabolism, including upregulation of lactate dehydrogenase and of many genes involved in the catabolism of fats and proteins, and various anaplerotic pathways. Gut-specific enzymes involved in the primary mobilization of dietary fats and proteins, as well as a number of transport functions, were also strongly up-regulated, consistent with the idea that oxidative phosphorylation OXPHOS dysfunction is perceived physiologically as a starvation for particular biomolecules. In addition, many stressresponse genes were induced. Other changes may reflect a signature of developmental delay, notably a down-regulation of genes connected with reproduction, including gametogenesis, as well as courtship behavior in males; logically this represents a programmed response to a mitochondrially generated starvation signal. The underlying signalling pathway, if conserved, could influence many physiological processes in response to nutritional stress, although any such pathway involved remains unidentified. Conclusions/Significance: These studies indicate that general and organ-specific metabolism is transformed in response to mitochondrial dysfunction, including digestive and absorptive functions, and give important clues as to how novel therapeutic strategies for mitochondrial disorders might be developed.
Current Biology, 2005
rich male peptides [5-7]. Sex-peptide (SP) and Ovulin are products of the accessory glands, and t... more rich male peptides [5-7]. Sex-peptide (SP) and Ovulin are products of the accessory glands, and the Ductus ejacu-Winterthurerstrasse 190 CH-8057 Zü rich latorius peptide (DUP) is synthesized in the ejaculatory duct. They are transferred together with sperm into the Switzerland female during mating [7]. SP and DUP induce both PMR. Ovulin elicits ovulation and oviposition on the first day after mating, but does not affect receptivity [8]. Mating Summary with wild-type males induces the PMR for about 1 week; however, mating with males that do not transfer sperm Background: In many female insects, peptides transelicits PMR only for one day (long-term and short-term ferred in the seminal fluid induce postmating responses PMR, respectively). (This phenomenon has been de-(PMR), such as a drastic increase of egg laying and scribed as "sperm effect" by Manning, [9, 10].) Males reduction of receptivity (readiness to mate). In Drosophlacking functional SP (SP 0 males) elicit only weak PMR ila melanogaster, sex-peptide (SP) elicits short-and lasting about one day [11, 12]. Hence, in vivo SP is the long-term PMR, but only the latter in the presence of major agent eliciting both the short-and the long-term stored sperm (sperm effect). PMR; Ovulin and DUP play only minor roles during the Results: Here, we elucidate the interaction between SP first day after copulation. Because SP 0 males transfer and sperm by immunofluorescence microscopy. Transand store sperm [12], sperm alone cannot induce the genic males were used to study the effects of SP modifi-PMR, but stored sperm are essential for their persiscation on the PMR of females in vivo. We report that tence [9, 10]. Without sperm transfer, or injection of SP binds to sperm with its N-terminal end. In females, physiological amounts of the peptide, SP elicits only the C-terminal part of SP known to be essential to induce short-term PMR [7, 10, 13]. How do SP and sperm interthe PMR is gradually released from stored sperm by act to support the long-term PMR? A possible mechacleavage at a trypsin cleavage site, thus prolonging the nism could be binding of SP to sperm [14]. Here, we PMR. These findings are confirmed by analyzing the show that SP binds to sperm with the N-terminal end. PMR elicited by males containing transgenes encoding During storage, SP is cleaved off from the tail, and the modified SPs. SP lacking the N-terminal end cannot released C-terminal part elicits the long-term PMR. bind, and SP without the trypsin cleavage site binds permanently to sperm. Conclusion: By binding to sperm tails, SP prolongs the Results PMR. Thus, besides a carrier for genetic information, sperm is also the carrier for SP. Binding to sperm may Sex-Peptide Binds to Sperm Stored protect the peptide from degradation by proteases in in the Genital Tract of the Female the hemolymph and, thus, prolong its half-life. Longer We used immunofluorescence to visualize putative sperm tails may transfer more SP and thus increase the binding of peptides to sperm. Sperm were isolated from reproductive fitness of the male. We suggest that this females at different time intervals after mating and were could explain the excessive length of sperm tails in some then incubated with antibodies specific for SP, DUP, or Drosophila species. Ovulin, respectively (Figure 1). DUP binds only to the head and only in the first few hours (data not shown), whereas Ovulin does not bind to sperm at all (Figure
Genetics, 2012
Phenotypes relevant to oxidative phosphorylation (OXPHOS) in eukaryotes are jointly determined by... more Phenotypes relevant to oxidative phosphorylation (OXPHOS) in eukaryotes are jointly determined by nuclear and mitochondrial DNA (mtDNA). Thus, in humans, the variable clinical presentations of mitochondrial disease patients bearing the same primary mutation, whether in nuclear or mitochondrial DNA, have been attributed to putative genetic determinants carried in the “other” genome, though their identity and the molecular mechanism(s) by which they might act remain elusive. Here we demonstrate cytoplasmic suppression of the mitochondrial disease-like phenotype of the Drosophila melanogaster nuclear mutant tko25t, which includes developmental delay, seizure sensitivity, and defective male courtship. The tko25t strain carries a mutation in a mitoribosomal protein gene, causing OXPHOS deficiency due to defective intramitochondrial protein synthesis. Phenotypic suppression was associated with increased mtDNA copy number and increased mitochondrial biogenesis, as measured by the expressio...