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Peiyuan Qian - One of the best experts on this subject based on the ideXlab platform.
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exploring the regulatory role of nitric oxide no and the no p38mapk cgmp pathway in larval settlement of the bryozoan Bugula neritina
Biofouling, 2018Co-Authors: Xiao-xue Yang, Yu Zhang, Yue Him Wong, Gen Zhang, Peiyuan QianAbstract:The bryozoan Bugula neritina is a cosmopolitan marine fouling species that causes major fouling problems in sub-tropical waters. Settlement of B. neritina larvae can be triggered without an obvious external cue. Here, the negative regulatory role of nitric oxide (NO) during larval settlement of B. neritina was demonstrated to be mediated by cyclic guanosine monophosphate (cGMP). Although the regulatory role of the NO-p38 MAPK signaling axis in larval settlement was not evident, inhibition of nitric oxide synthase (NOS) led to the deactivation of p38 MAPK. Exclusive localization of NO and NO signaling components in sensory-related organs of the larvae is consistent with its signal transduction function in metamorphosis. Overall, this study provides new insights into the regulatory roles of the NO-p38MAPK/cGMP pathway in B. neritina settlement.
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Exploring the regulatory role of nitric oxide (NO) and the NO-p38MAPK/cGMP pathway in larval settlement of the bryozoan Bugula neritina
Biofouling, 2018Co-Authors: Xiao-xue Yang, Yu Zhang, Yue Him Wong, Zhang, Peiyuan QianAbstract:The bryozoan Bugula neritina is a cosmopolitan marine fouling species that causes major fouling problems in sub-tropical waters. Settlement of B. neritina larvae can be triggered without an obvious external cue. Here, the negative regulatory role of nitric oxide (NO) during larval settlement of B. neritina was demonstrated to be mediated by cyclic guanosine monophosphate (cGMP). Although the regulatory role of the NO-p38 MAPK signaling axis in larval settlement was not evident, inhibition of nitric oxide synthase (NOS) led to the deactivation of p38 MAPK. Exclusive localization of NO and NO signaling components in sensory-related organs of the larvae is consistent with its signal transduction function in metamorphosis. Overall, this study provides new insights into the regulatory roles of the NO-p38MAPK/cGMP pathway in B. neritina settlement.
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In Silico Prediction of Neuropeptides/Peptide Hormone Transcripts in the Cheilostome Bryozoan Bugula neritina
PloS one, 2016Co-Authors: Yue Him Wong, Zhang, Peiyuan QianAbstract:The bryozoan Bugula neritina has a biphasic life cycle that consists of a planktonic larval stage and a sessile juvenile/adult stage. The transition between these two stages is crucial for the development and recruitment of B. neritina. Metamorphosis in B. neritina is mediated by both the nervous system and the release of developmental signals. However, no research has been conducted to investigate the expression of neuropeptides (NP)/peptide hormones in B. neritina larvae. Here, we report a comprehensive study of the NP/peptide hormones in the marine bryozoan B. neritina based on in silico identification methods. We recovered 22 transcripts encompassing 11 NP/peptide hormone precursor transcript sequences. The transcript sequences of the 11 isolated NP precursors were validated by cDNA cloning using gene-specific primers. We also examined the expression of three peptide hormone precursor transcripts (BnFDSIG, BnILP1, BnGPB) in the coronate larvae of B. neritina, demonstrating their distinct expression patterns in the larvae. Overall, our findings serve as an important foundation for subsequent investigations of the peptidergic control of bryozoan larval behavior and settlement.
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in silico prediction of neuropeptides peptide hormone transcripts in the cheilostome bryozoan Bugula neritina
PLOS ONE, 2016Co-Authors: Yue Him Wong, Peiyuan Qian, Gen ZhangAbstract:The bryozoan Bugula neritina has a biphasic life cycle that consists of a planktonic larval stage and a sessile juvenile/adult stage. The transition between these two stages is crucial for the development and recruitment of B. neritina. Metamorphosis in B. neritina is mediated by both the nervous system and the release of developmental signals. However, no research has been conducted to investigate the expression of neuropeptides (NP)/peptide hormones in B. neritina larvae. Here, we report a comprehensive study of the NP/peptide hormones in the marine bryozoan B. neritina based on in silico identification methods. We recovered 22 transcripts encompassing 11 NP/peptide hormone precursor transcript sequences. The transcript sequences of the 11 isolated NP precursors were validated by cDNA cloning using gene-specific primers. We also examined the expression of three peptide hormone precursor transcripts (BnFDSIG, BnILP1, BnGPB) in the coronate larvae of B. neritina, demonstrating their distinct expression patterns in the larvae. Overall, our findings serve as an important foundation for subsequent investigations of the peptidergic control of bryozoan larval behavior and settlement.
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the mode of action of isocyanide in three aquatic organisms balanus amphitrite Bugula neritina and danio rerio
PLOS ONE, 2012Co-Authors: Yoshikazu Kitano, Yu Zhang, Yasuyuki Nogata, Peiyuan QianAbstract:Isocyanide is a potential antifouling compound in marine environments. In this study, we investigated its mode of action in three aquatic organisms. Two of them, the bryozoan Bugula neritina and the barnacle Balanus amphitrite, are major marine fouling invertebrates, and the other organism is the non-target species zebrafish Danio rerio. In the swimming larvae of B. neritina, isocyanide did not affect the total attachment rate (≤50 µg ml−1), but it did change the attachment site by increasing the percentage of attachment on the bottom of the container rather than on the wall or air-water inter-surface. Isocyanide binds several proteins in B. neritina as identified via SDS-PAGE-LC-MS/MS: 1) a 30 kD protein band containing two proteins similar to voltage dependent anion channels (VDAC), which control the direct coupling of the mitochondrial matrix to the energy maintenance of the cytosol and the release of apoptogenic factors from mitochondria of mammalian cells; and 2) an unknown 39 kD protein. In B. amphitrite cyprids, the isocyanide binding protein were 1) a protein similar to NADH-ubiquinone oxidoreductase, which is the “entry enzyme” of oxidative phosphorylation in mitochondria; and 2) cytochrome P450. In Danio rerio embryos, isocyanide caused “wavy” notochords, hydrocephalus, pericardial edema, poor blood circulation, and defects in pigmentation and hematopoiesis, which phenocopied copper deficiency. This is the first report on isocyanide binding proteins in fouling organisms, as well as the first description of its phenotype and potential toxicology in zebrafish.
Yue Him Wong - One of the best experts on this subject based on the ideXlab platform.
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exploring the regulatory role of nitric oxide no and the no p38mapk cgmp pathway in larval settlement of the bryozoan Bugula neritina
Biofouling, 2018Co-Authors: Xiao-xue Yang, Yu Zhang, Yue Him Wong, Gen Zhang, Peiyuan QianAbstract:The bryozoan Bugula neritina is a cosmopolitan marine fouling species that causes major fouling problems in sub-tropical waters. Settlement of B. neritina larvae can be triggered without an obvious external cue. Here, the negative regulatory role of nitric oxide (NO) during larval settlement of B. neritina was demonstrated to be mediated by cyclic guanosine monophosphate (cGMP). Although the regulatory role of the NO-p38 MAPK signaling axis in larval settlement was not evident, inhibition of nitric oxide synthase (NOS) led to the deactivation of p38 MAPK. Exclusive localization of NO and NO signaling components in sensory-related organs of the larvae is consistent with its signal transduction function in metamorphosis. Overall, this study provides new insights into the regulatory roles of the NO-p38MAPK/cGMP pathway in B. neritina settlement.
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Exploring the regulatory role of nitric oxide (NO) and the NO-p38MAPK/cGMP pathway in larval settlement of the bryozoan Bugula neritina
Biofouling, 2018Co-Authors: Xiao-xue Yang, Yu Zhang, Yue Him Wong, Zhang, Peiyuan QianAbstract:The bryozoan Bugula neritina is a cosmopolitan marine fouling species that causes major fouling problems in sub-tropical waters. Settlement of B. neritina larvae can be triggered without an obvious external cue. Here, the negative regulatory role of nitric oxide (NO) during larval settlement of B. neritina was demonstrated to be mediated by cyclic guanosine monophosphate (cGMP). Although the regulatory role of the NO-p38 MAPK signaling axis in larval settlement was not evident, inhibition of nitric oxide synthase (NOS) led to the deactivation of p38 MAPK. Exclusive localization of NO and NO signaling components in sensory-related organs of the larvae is consistent with its signal transduction function in metamorphosis. Overall, this study provides new insights into the regulatory roles of the NO-p38MAPK/cGMP pathway in B. neritina settlement.
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HSP90 regulates larval settlement of the bryozoan Bugula neritina through the nitric oxide pathway.
The Journal of Experimental Biology, 2018Co-Authors: Xiao-xue Yang, Yu Zhang, Yue Him WongAbstract:ABSTRACT The larvae of many sessile marine invertebrates go through a settlement process, during which planktonic larvae attach to a substrate and metamorphose into sessile juveniles. Larval attachment and metamorphosis (herein defined as ‘settlement’) are complex processes mediated by many signalling pathways. Nitric oxide (NO) signalling is one of the pathways that inhibits larval settlement in marine invertebrates across different phyla. NO is synthesized by NO synthase (NOS), which is a client of the molecular chaperone heat shock protein 90 (HSP90). In the present study, we provide evidence that NO, a gaseous messenger, regulates larval settlement of Bugula neritina . By using pharmacological bioassays and western blotting, we demonstrated that NO inhibits larval settlement of B. neritina and that NO signals occur mainly in the sensory organ of swimming larvae. The settlement rate of B. neritina larvae decreased after heat shock treatment. Inhibition of HSP90 induced larval settlement, and attenuated the inhibition of NO donors during larval settlement. In addition, the expression level of both HSP90 and NOS declined upon settlement. These results demonstrate that HSP90 regulates the larval settlement of B. neritina by interacting with the NO pathway.
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The regulatory role of arginine kinase during larval settlement of the bryozoan Bugula neritina
Marine Biology, 2018Co-Authors: Yu Zhang, Xiao-xue Yang, Yue Him WongAbstract:Larval attachment and metamorphosis, also collectively known as settlement, plays an important role in the life history of marine invertebrates with biphasic life cycle. Bugula neritina can settle on any substrate without substrate selection. This complex transformation usually involves an active selection process, while the larval decision to settle is regulated by both exogenous and endogenous factors. This study focuses on the involvement of arginine kinase (AK), an important enzyme that regulates energy metabolism in marine invertebrates, during larval settlement of the bryozoan Bugula neritina. We reveal that AK was highly expressed in the swimming larvae of B. neritina, while its expression was down-regulated post-attachment. When treated with AK inhibitors, the larval settlement rate was significantly decreased. In addition, the immunostaining results indicated that AK was mainly localized to the neuro-muscular cord in swimming larvae. Overall, our results suggest the involvement of AK in regulating larval settlement of B. neritina.
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in silico prediction of neuropeptides peptide hormone transcripts in the cheilostome bryozoan Bugula neritina
PLOS ONE, 2016Co-Authors: Yue Him Wong, Peiyuan Qian, Gen ZhangAbstract:The bryozoan Bugula neritina has a biphasic life cycle that consists of a planktonic larval stage and a sessile juvenile/adult stage. The transition between these two stages is crucial for the development and recruitment of B. neritina. Metamorphosis in B. neritina is mediated by both the nervous system and the release of developmental signals. However, no research has been conducted to investigate the expression of neuropeptides (NP)/peptide hormones in B. neritina larvae. Here, we report a comprehensive study of the NP/peptide hormones in the marine bryozoan B. neritina based on in silico identification methods. We recovered 22 transcripts encompassing 11 NP/peptide hormone precursor transcript sequences. The transcript sequences of the 11 isolated NP precursors were validated by cDNA cloning using gene-specific primers. We also examined the expression of three peptide hormone precursor transcripts (BnFDSIG, BnILP1, BnGPB) in the coronate larvae of B. neritina, demonstrating their distinct expression patterns in the larvae. Overall, our findings serve as an important foundation for subsequent investigations of the peptidergic control of bryozoan larval behavior and settlement.
Margo G. Haygood - One of the best experts on this subject based on the ideXlab platform.
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localization of candidatus endoBugula sertula and the bryostatins throughout the life cycle of the bryozoan Bugula neritina
The ISME Journal, 2007Co-Authors: Seana K Davidson, Koty H. Sharp, Margo G. HaygoodAbstract:‘Candidatus EndoBugula sertula,’ the uncultivated γ-proteobacterial symbiont of the marine bryozoan Bugula neritina, synthesizes bryostatins, complex polyketides that render B. neritina larvae unpalatable to predators. Although the symbiosis is well described, little is known about the locations of ‘E. sertula’ or the bryostatins throughout larval settlement, metamorphosis and early development. In this study, we simultaneously localized ‘E. sertula’ and the bryostatins in multiple stages of the B. neritina life cycle, using a novel bryostatin detection method based on its known ability to bind mammalian protein kinase C. Our results suggest that the bryostatins are deposited onto the exterior of B. neritina larvae during embryonic development, persist on the larval surface throughout metamorphosis and are shed prior to cuticle formation. During metamorphosis, ‘E. sertula’ remains adhered to the larval pallial epithelium and is incorporated into the preancestrula cystid tissue layer, which ultimately develops into a bud and gives rise to the next zooid in the colony. Colocalization of bryostatin signal with aggregates of ‘E. sertula’ in buds of ancestrulae suggested new synthesis of bryostatins in ancestrulae. In adult B. neritina colonies, symbiont microcolonies were observed in the funicular cords of rhizoids, which likely result in asexual transmission of ‘E. sertula’ to regenerated colonies. Furthermore, bryostatin signal was detected on the surface of the rhizoids of adult B. neritina colonies. Through simultaneous localization of the bryostatins and the ‘E. sertula,’ we determined how ‘E. sertula’ is transmitted, and identified shifts in bryostatin localization throughout the life cycle of the host B. neritina.
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identification of the putative bryostatin polyketide synthase gene cluster from candidatus endoBugula sertula the uncultivated microbial symbiont of the marine bryozoan Bugula neritina
Journal of Natural Products, 2007Co-Authors: Sebastian Sudek, Christine Anderson, Nicole B. Lopanik, Laura E Waggoner, Mark Hildebrand, Haibin Liu, Amrish Patel, David H Sherman, Margo G. HaygoodAbstract:The bryostatins are protein kinase C modulators with unique structural features and potential anticancer and neurological activities. These complex polyketides were isolated from the marine bryozoan Bugula neritina, but recent studies indicate that they are produced by the uncultured symbiotic bacterium "Candidatus EndoBugula sertula" ("E. sertula"). Here we present the putative biosynthetic genes: five modular polyketide synthase (PKS) genes, a discrete acyltransferase, a beta-ketosynthase, a hydroxy-methyl-glutaryl CoA synthase (HMG-CS), and a methyltransferase. The cluster was sequenced in two closely related "E. sertula" strains from different host species. In one strain the gene cluster is contiguous, while in the other strain it is split into two loci, with one locus containing the PKS genes and the other containing the accessory genes. Here, we propose a hypothesis for the biosynthesis of the bryostatins. Thirteen PKS modules form the core macrolactone ring, and the pendent methyl ester groups are added by the HMG-CS gene cassette. The resulting hypothetical compound bryostatin 0 is the common basis for the 20 known bryostatins. As "E. sertula" is to date uncultured, heterologous expression of this biosynthetic gene cluster has the potential of producing the bioactive bryostatins in large enough quantities for development into a pharmaceutical.
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identification of the putative bryostatin polyketide synthase gene cluster from candidatus endoBugula sertula the uncultivated microbial symbiont of the marine bryozoan Bugula neritina
Journal of Natural Products, 2007Co-Authors: Sebastian Sudek, Christine Anderson, Nicole B. Lopanik, Laura E Waggoner, Mark Hildebrand, Haibin Liu, Amrish Patel, David H Sherman, Margo G. HaygoodAbstract:The bryostatins are protein kinase C modulators with unique structural features and potential anticancer and neurological activities. These complex polyketides were isolated from the marine bryozoan Bugula neritina, but recent studies indicate that they are produced by the uncultured symbiotic bacterium “Candidatus EndoBugula sertula” (“E. sertula”). Here we present the putative biosynthetic genes: five modular polyketide synthase (PKS) genes, a discrete acyltransferase, a β-ketosynthase, a hydroxy-methyl-glutaryl CoA synthase (HMG-CS), and a methyltransferase. The cluster was sequenced in two closely related “E. sertula” strains from different host species. In one strain the gene cluster is contiguous, while in the other strain it is split into two loci, with one locus containing the PKS genes and the other containing the accessory genes. Here, we propose a hypothesis for the biosynthesis of the bryostatins. Thirteen PKS modules form the core macrolactone ring, and the pendent methyl ester groups are ad...
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brya an unusual modular polyketide synthase gene from the uncultivated bacterial symbiont of the marine bryozoan Bugula neritina
Chemistry & Biology, 2004Co-Authors: Mark Hildebrand, Christine Anderson, Sebastian Sudek, Laura E Waggoner, Haibin Liu, David H Sherman, Scott Allen, Margo G. HaygoodAbstract:"Candidatus EndoBugula sertula," the uncultivated bacterial symbiont of Bugula neritina, is the proposed source of the bryostatin family of anticancer compounds. We cloned a large modular polyketide synthase (PKS) gene complex from "Candidatus EndoBugula sertula" and characterized one gene, bryA, which we propose is responsible for the initial steps of bryostatin biosynthesis. Typical PKS domains are present. However, acyltransferase domains are lacking in bryA, and beta-ketoacyl synthase domains of bryA cluster with those of PKSs with discrete, rather than integral, acyltransferases. We propose a model for biosynthesis of the bryostatin D-lactate starter unit by the bryA loading module, utilizing atypical domains homologous to FkbH, KR, and DH. The bryA gene product is proposed to synthesize a portion of the pharmacologically active part of bryostatin and may be useful in semisynthesis of clinically useful bryostatin analogs.
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evidence for the biosynthesis of bryostatins by the bacterial symbiont candidatus endoBugula sertula of the bryozoan Bugula neritina
Applied and Environmental Microbiology, 2001Co-Authors: Seana K Davidson, Scott W Allen, Christine Anderson, Margo G. HaygoodAbstract:The marine bryozoan, Bugula neritina, is the source of the bryostatins, a family of macrocyclic lactones with anticancer activity. Bryostatins have long been suspected to be bacterial products. B. neritina harbors the uncultivated gamma proteobacterial symbiont “Candidatus EndoBugula sertula.” In this work several lines of evidence are presented that show that the symbiont is the most likely source of bryostatins. Bryostatins are complex polyketides similar to bacterial secondary metabolites synthesized by modular type I polyketide synthases (PKS-I). PKS-I gene fragments were cloned from DNA extracted from the B. neritina-“E. sertula” association, and then primers specific to one of these clones, KSa, were shown to amplify the KSa gene specifically and universally from total B. neritina DNA. In addition, a KSa RNA probe was shown to bind specifically to the symbiotic bacteria located in the pallial sinus of the larvae of B. neritina and not to B. neritina cells or to other bacteria. Finally, B. neritina colonies grown in the laboratory were treated with antibiotics to reduce the numbers of bacterial symbionts. Decreased symbiont levels resulted in the reduction of the KSa signal as well as the bryostatin content. These data provide evidence that the symbiont E. sertula has the genetic potential to make bryostatins and is necessary in full complement for the host bryozoan to produce normal levels of bryostatins. This study demonstrates that it may be possible to clone bryostatin genes from B. neritina directly and use these to produce bryostatins in heterologous host bacteria.
Yu Zhang - One of the best experts on this subject based on the ideXlab platform.
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exploring the regulatory role of nitric oxide no and the no p38mapk cgmp pathway in larval settlement of the bryozoan Bugula neritina
Biofouling, 2018Co-Authors: Xiao-xue Yang, Yu Zhang, Yue Him Wong, Gen Zhang, Peiyuan QianAbstract:The bryozoan Bugula neritina is a cosmopolitan marine fouling species that causes major fouling problems in sub-tropical waters. Settlement of B. neritina larvae can be triggered without an obvious external cue. Here, the negative regulatory role of nitric oxide (NO) during larval settlement of B. neritina was demonstrated to be mediated by cyclic guanosine monophosphate (cGMP). Although the regulatory role of the NO-p38 MAPK signaling axis in larval settlement was not evident, inhibition of nitric oxide synthase (NOS) led to the deactivation of p38 MAPK. Exclusive localization of NO and NO signaling components in sensory-related organs of the larvae is consistent with its signal transduction function in metamorphosis. Overall, this study provides new insights into the regulatory roles of the NO-p38MAPK/cGMP pathway in B. neritina settlement.
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Exploring the regulatory role of nitric oxide (NO) and the NO-p38MAPK/cGMP pathway in larval settlement of the bryozoan Bugula neritina
Biofouling, 2018Co-Authors: Xiao-xue Yang, Yu Zhang, Yue Him Wong, Zhang, Peiyuan QianAbstract:The bryozoan Bugula neritina is a cosmopolitan marine fouling species that causes major fouling problems in sub-tropical waters. Settlement of B. neritina larvae can be triggered without an obvious external cue. Here, the negative regulatory role of nitric oxide (NO) during larval settlement of B. neritina was demonstrated to be mediated by cyclic guanosine monophosphate (cGMP). Although the regulatory role of the NO-p38 MAPK signaling axis in larval settlement was not evident, inhibition of nitric oxide synthase (NOS) led to the deactivation of p38 MAPK. Exclusive localization of NO and NO signaling components in sensory-related organs of the larvae is consistent with its signal transduction function in metamorphosis. Overall, this study provides new insights into the regulatory roles of the NO-p38MAPK/cGMP pathway in B. neritina settlement.
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HSP90 regulates larval settlement of the bryozoan Bugula neritina through the nitric oxide pathway.
The Journal of Experimental Biology, 2018Co-Authors: Xiao-xue Yang, Yu Zhang, Yue Him WongAbstract:ABSTRACT The larvae of many sessile marine invertebrates go through a settlement process, during which planktonic larvae attach to a substrate and metamorphose into sessile juveniles. Larval attachment and metamorphosis (herein defined as ‘settlement’) are complex processes mediated by many signalling pathways. Nitric oxide (NO) signalling is one of the pathways that inhibits larval settlement in marine invertebrates across different phyla. NO is synthesized by NO synthase (NOS), which is a client of the molecular chaperone heat shock protein 90 (HSP90). In the present study, we provide evidence that NO, a gaseous messenger, regulates larval settlement of Bugula neritina . By using pharmacological bioassays and western blotting, we demonstrated that NO inhibits larval settlement of B. neritina and that NO signals occur mainly in the sensory organ of swimming larvae. The settlement rate of B. neritina larvae decreased after heat shock treatment. Inhibition of HSP90 induced larval settlement, and attenuated the inhibition of NO donors during larval settlement. In addition, the expression level of both HSP90 and NOS declined upon settlement. These results demonstrate that HSP90 regulates the larval settlement of B. neritina by interacting with the NO pathway.
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The regulatory role of arginine kinase during larval settlement of the bryozoan Bugula neritina
Marine Biology, 2018Co-Authors: Yu Zhang, Xiao-xue Yang, Yue Him WongAbstract:Larval attachment and metamorphosis, also collectively known as settlement, plays an important role in the life history of marine invertebrates with biphasic life cycle. Bugula neritina can settle on any substrate without substrate selection. This complex transformation usually involves an active selection process, while the larval decision to settle is regulated by both exogenous and endogenous factors. This study focuses on the involvement of arginine kinase (AK), an important enzyme that regulates energy metabolism in marine invertebrates, during larval settlement of the bryozoan Bugula neritina. We reveal that AK was highly expressed in the swimming larvae of B. neritina, while its expression was down-regulated post-attachment. When treated with AK inhibitors, the larval settlement rate was significantly decreased. In addition, the immunostaining results indicated that AK was mainly localized to the neuro-muscular cord in swimming larvae. Overall, our results suggest the involvement of AK in regulating larval settlement of B. neritina.
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the mode of action of isocyanide in three aquatic organisms balanus amphitrite Bugula neritina and danio rerio
PLOS ONE, 2012Co-Authors: Yoshikazu Kitano, Yu Zhang, Yasuyuki Nogata, Peiyuan QianAbstract:Isocyanide is a potential antifouling compound in marine environments. In this study, we investigated its mode of action in three aquatic organisms. Two of them, the bryozoan Bugula neritina and the barnacle Balanus amphitrite, are major marine fouling invertebrates, and the other organism is the non-target species zebrafish Danio rerio. In the swimming larvae of B. neritina, isocyanide did not affect the total attachment rate (≤50 µg ml−1), but it did change the attachment site by increasing the percentage of attachment on the bottom of the container rather than on the wall or air-water inter-surface. Isocyanide binds several proteins in B. neritina as identified via SDS-PAGE-LC-MS/MS: 1) a 30 kD protein band containing two proteins similar to voltage dependent anion channels (VDAC), which control the direct coupling of the mitochondrial matrix to the energy maintenance of the cytosol and the release of apoptogenic factors from mitochondria of mammalian cells; and 2) an unknown 39 kD protein. In B. amphitrite cyprids, the isocyanide binding protein were 1) a protein similar to NADH-ubiquinone oxidoreductase, which is the “entry enzyme” of oxidative phosphorylation in mitochondria; and 2) cytochrome P450. In Danio rerio embryos, isocyanide caused “wavy” notochords, hydrocephalus, pericardial edema, poor blood circulation, and defects in pigmentation and hematopoiesis, which phenocopied copper deficiency. This is the first report on isocyanide binding proteins in fouling organisms, as well as the first description of its phenotype and potential toxicology in zebrafish.
Nicole B. Lopanik - One of the best experts on this subject based on the ideXlab platform.
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influence of symbiont produced bioactive natural products on holobiont fitness in the marine bryozoan Bugula neritina via protein kinase c pkc
Marine Biology, 2016Co-Authors: Meril Mathew, Nicole B. Lopanik, Kayla I Bean, Yvette Tematetiagueu, Adrian Caciula, Ion I Mandoiu, Alexander ZelikovskyAbstract:Marine invertebrates are a major source of bioactive natural products, many of which are produced by associated microbes. These compounds protect the invertebrate host against predators, competitors, or pathogens by affecting the cellular processes of the host’s adversary, but knowledge about the interaction of the host itself with these symbiont-produced natural products is limited. For example, larvae of the marine bryozoan, Bugula neritina, are defended from predation by the bryostatins, polyketides synthesized by its uncultured endosymbiont, “Candidatus EndoBugula sertula.” Bryostatins are potent modulators of the eukaryotic signaling protein, protein kinase C (PKC) that is involved in many cellular processes. In this study, we investigated how host reproduction responds to the absence of the symbiont and symbiont-produced bryostatins in colonies after antibiotic curing and in colonies with naturally reduced symbiont titers. The fecundity of the symbiont-reduced B. neritina colonies was significantly decreased, suggesting that host reproduction is dependent on the symbiont, and/or the bryostatins they produce. To assess the role of PKC in this response, Western blot analysis of protein extracts from symbiotic and symbiont-reduced B. neritina colonies revealed a difference in bryostatin-activated conventional PKCs, but none for bryostatin-independent PKCs. Similar results were observed for PKCs in symbiotic and naturally occurring symbiont-reduced colonies, as well as in the model invertebrate, Caenorhabditis elegans, exposed to bryostatin, suggesting that the bryostatins potentially modulate PKC activity in symbiotic B. neritina and bryostatin-exposed C. elegans. Analysis of the B. neritina transcriptome led to the identification of five PKC isozymes. Since PKCs have been reported to be involved in regulation of reproductive processes and oocyte maturation in various organisms, the findings of this study suggest that the symbiont-produced bryostatins are an important cue for reproduction in the host B. neritina via PKC activation.
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latitudinal variation of a defensive symbiosis in the Bugula neritina bryozoa sibling species complex
PLOS ONE, 2014Co-Authors: Jonathan Linneman, Grace Limfong, Darcy Paulus, Nicole B. LopanikAbstract:Mutualistic relationships are beneficial for both partners and are often studied within a single environment. However, when the range of the partners is large, geographical differences in selective pressure may shift the relationship outcome from positive to negative. The marine bryozoan Bugula neritina is a colonial invertebrate common in temperate waters worldwide. It is the source of bioactive polyketide metabolites, the bryostatins. Evidence suggests that an uncultured vertically transmitted symbiont, “Candidatus EndoBugula sertula”, hosted by B. neritina produces the bryostatins, which protect the vulnerable larvae from predation. Studies of B. neritina along the North American Atlantic coast revealed a complex of two morphologically similar sibling species separated by an apparent biogeographic barrier: the Type S sibling species was found below Cape Hatteras, North Carolina, while Type N was found above. Interestingly, the Type N colonies lack “Ca. EndoBugula sertula” and, subsequently, defensive bryostatins; their documented northern distribution was consistent with traditional biogeographical paradigms of latitudinal variation in predation pressure. Upon further sampling of B. neritina populations, we found that both host types occur in wider distribution, with Type N colonies living south of Cape Hatteras, and Type S to the north. Distribution of the symbiont, however, was not restricted to Type S hosts. Genetic and microscopic evidence demonstrates the presence of the symbiont in some Type N colonies, and larvae from these colonies are endowed with defensive bryostatins and contain “Ca. EndoBugula sertula”. Molecular analysis of the symbiont from Type N colonies suggests an evolutionarily recent acquisition, which is remarkable for a symbiont thought to be transmitted only vertically. Furthermore, most Type S colonies found at higher latitudes lack the symbiont, suggesting that this host-symbiont relationship is more flexible than previously thought. Our data suggest that the symbiont, but not the host, is restricted by biogeographical boundaries.
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identification of the putative bryostatin polyketide synthase gene cluster from candidatus endoBugula sertula the uncultivated microbial symbiont of the marine bryozoan Bugula neritina
Journal of Natural Products, 2007Co-Authors: Sebastian Sudek, Christine Anderson, Nicole B. Lopanik, Laura E Waggoner, Mark Hildebrand, Haibin Liu, Amrish Patel, David H Sherman, Margo G. HaygoodAbstract:The bryostatins are protein kinase C modulators with unique structural features and potential anticancer and neurological activities. These complex polyketides were isolated from the marine bryozoan Bugula neritina, but recent studies indicate that they are produced by the uncultured symbiotic bacterium "Candidatus EndoBugula sertula" ("E. sertula"). Here we present the putative biosynthetic genes: five modular polyketide synthase (PKS) genes, a discrete acyltransferase, a beta-ketosynthase, a hydroxy-methyl-glutaryl CoA synthase (HMG-CS), and a methyltransferase. The cluster was sequenced in two closely related "E. sertula" strains from different host species. In one strain the gene cluster is contiguous, while in the other strain it is split into two loci, with one locus containing the PKS genes and the other containing the accessory genes. Here, we propose a hypothesis for the biosynthesis of the bryostatins. Thirteen PKS modules form the core macrolactone ring, and the pendent methyl ester groups are added by the HMG-CS gene cassette. The resulting hypothetical compound bryostatin 0 is the common basis for the 20 known bryostatins. As "E. sertula" is to date uncultured, heterologous expression of this biosynthetic gene cluster has the potential of producing the bioactive bryostatins in large enough quantities for development into a pharmaceutical.
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identification of the putative bryostatin polyketide synthase gene cluster from candidatus endoBugula sertula the uncultivated microbial symbiont of the marine bryozoan Bugula neritina
Journal of Natural Products, 2007Co-Authors: Sebastian Sudek, Christine Anderson, Nicole B. Lopanik, Laura E Waggoner, Mark Hildebrand, Haibin Liu, Amrish Patel, David H Sherman, Margo G. HaygoodAbstract:The bryostatins are protein kinase C modulators with unique structural features and potential anticancer and neurological activities. These complex polyketides were isolated from the marine bryozoan Bugula neritina, but recent studies indicate that they are produced by the uncultured symbiotic bacterium “Candidatus EndoBugula sertula” (“E. sertula”). Here we present the putative biosynthetic genes: five modular polyketide synthase (PKS) genes, a discrete acyltransferase, a β-ketosynthase, a hydroxy-methyl-glutaryl CoA synthase (HMG-CS), and a methyltransferase. The cluster was sequenced in two closely related “E. sertula” strains from different host species. In one strain the gene cluster is contiguous, while in the other strain it is split into two loci, with one locus containing the PKS genes and the other containing the accessory genes. Here, we propose a hypothesis for the biosynthesis of the bryostatins. Thirteen PKS modules form the core macrolactone ring, and the pendent methyl ester groups are ad...
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ontogeny of a symbiont produced chemical defense in Bugula neritina bryozoa
Marine Ecology Progress Series, 2006Co-Authors: Nicole B. Lopanik, Nancy M Targett, Niels LindquistAbstract:The larvae of the arborescent bryozoan Bugula neritina are chemically defended against predators by unpalatable secondary metabolites called bryostatins. Bryostatins, polyketide- derived secondary compounds, are produced by the bacterial symbiont 'Candidatus EndoBugula sertula', which is present throughout all life stages of B. neritina. Crude extracts of larval and all juve- nile stages of B. neritina significantly reduced pinfish feeding (p < 0.003). Extract unpalatability is due to high bryostatin concentrations. As B. neritina increases in age after larval settlement and metamor- phosis, palatability increases as bryostatin concentrations decrease precipitously. Extracts of brood- ing portions of adult colonies reduced pinfish feeding by a significant 54% (p = 0.008), whereas ex- tracts of non-brooding portions of the same colonies resulted in a non-significant 20% decline in feeding (p = 0.125). Our data suggest that the different life stages of B. neritina employ alternate de- fensive strategies. The mobile, short-lived larvae and early-stage juveniles are defended from preda- tors by having deterrent levels of bryostatins; in contrast, the older juveniles and adults, which are clonal and relatively long-lived, may be defended largely by high levels of structural material (i.e. chitin and carbonate). Predation pressure on the vulnerable larval stage of B. neritina appears in part to have driven selection for the development and maintenance of the symbiotic relationship between B. neritina and Ca. EndoBugula sertula whereby the larvae are chemically defended by symbiont- produced bryostatins.
