Transcriptional profiles in zebrafish atp7a mutants and responses of atp7a mutants to Cu stress
As a copper (Cu) transport ATPase, ATP7A plays an important role in maintaining Cu homeostasis in the body, but the developmental and physiological roles of atp7a in zebrafish embryogenesis are rarely studied. In this study, normal morphological phenotypes of atp7a−/− homozygous zebrafish were obser...
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KeAi Communications Co. Ltd.
2023-07-01
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| Series: | Water Biology and Security |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772735123000665 |
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| author | You Wu Wenye Liu Lingya Li Zhipeng Tai Jing-Xia Liu |
| author_facet | You Wu Wenye Liu Lingya Li Zhipeng Tai Jing-Xia Liu |
| author_sort | You Wu |
| collection | DOAJ |
| description | As a copper (Cu) transport ATPase, ATP7A plays an important role in maintaining Cu homeostasis in the body, but the developmental and physiological roles of atp7a in zebrafish embryogenesis are rarely studied. In this study, normal morphological phenotypes of atp7a−/− homozygous zebrafish were observed at both embryonic and adult stages, however, atp7a−/− larvae exhibited delayed touch response and obvious transcriptome changes. Compared with the WT (wild type), differentially expressed genes (DEGs) in atp7a−/− larvae showed the enrichment in gene ontology (GO) terms related to several processes including ATPase activity, oxidoreductase activity, active transmembrane transporter activity, ion binding, and the citrate cycle. Furthermore, decreases in both ATP content and Na+/K+-ATPase activity in atp7a−/− embryos and larvae were unveiled. 57 overlapping DEGs were found both in WT stressed with Cu and in WT mutated with atp7a, and GO term analysis indicated the enrichment in the genes related to neurexin family protein binding and neuronal cell-cell adhesion. Moreover, 42 overlapping DEGs in Cu stressed WT and Cu stressed atp7a−/− were identified. GO term analysis showed an enrichment in the genes related to heme binding, implying that Cu was independent of the integral function of atp7a to affect heme binding. In addition, genes involved in the negative regulation of angiogenesis were down-regulated in atp7a−/− mutants with and without Cu stress, which failed to occur in WT, implying that the integral function of atp7a is required for maintaining the normal expression of angiogenesis genes. The integrative data in this study demonstrated that atp7a is required for ion transport and angiogenesis, and for Cu-induced neurexin family protein binding defects, rather than for Cu-induced heme binding defects, during zebrafish embryogenesis. These findings provide possible clues for human diseases with ATP7A dysfunction and imbalanced Cu homeostasis. |
| first_indexed | 2024-03-13T02:55:38Z |
| format | Article |
| id | doaj.art-85ff397da3244429802cbffe13676f7b |
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| language | English |
| last_indexed | 2024-03-13T02:55:38Z |
| publishDate | 2023-07-01 |
| publisher | KeAi Communications Co. Ltd. |
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| series | Water Biology and Security |
| spelling | doaj.art-85ff397da3244429802cbffe13676f7b2023-06-28T04:30:44ZengKeAi Communications Co. Ltd.Water Biology and Security2772-73512023-07-0123100186Transcriptional profiles in zebrafish atp7a mutants and responses of atp7a mutants to Cu stressYou Wu0Wenye Liu1Lingya Li2Zhipeng Tai3Jing-Xia Liu4College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, 430070, ChinaCollege of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, 430070, ChinaCollege of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, 430070, ChinaCollege of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, 430070, ChinaCorresponding author. Huazhong Agricultural University, Wuhan, 430070, China.; College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, 430070, ChinaAs a copper (Cu) transport ATPase, ATP7A plays an important role in maintaining Cu homeostasis in the body, but the developmental and physiological roles of atp7a in zebrafish embryogenesis are rarely studied. In this study, normal morphological phenotypes of atp7a−/− homozygous zebrafish were observed at both embryonic and adult stages, however, atp7a−/− larvae exhibited delayed touch response and obvious transcriptome changes. Compared with the WT (wild type), differentially expressed genes (DEGs) in atp7a−/− larvae showed the enrichment in gene ontology (GO) terms related to several processes including ATPase activity, oxidoreductase activity, active transmembrane transporter activity, ion binding, and the citrate cycle. Furthermore, decreases in both ATP content and Na+/K+-ATPase activity in atp7a−/− embryos and larvae were unveiled. 57 overlapping DEGs were found both in WT stressed with Cu and in WT mutated with atp7a, and GO term analysis indicated the enrichment in the genes related to neurexin family protein binding and neuronal cell-cell adhesion. Moreover, 42 overlapping DEGs in Cu stressed WT and Cu stressed atp7a−/− were identified. GO term analysis showed an enrichment in the genes related to heme binding, implying that Cu was independent of the integral function of atp7a to affect heme binding. In addition, genes involved in the negative regulation of angiogenesis were down-regulated in atp7a−/− mutants with and without Cu stress, which failed to occur in WT, implying that the integral function of atp7a is required for maintaining the normal expression of angiogenesis genes. The integrative data in this study demonstrated that atp7a is required for ion transport and angiogenesis, and for Cu-induced neurexin family protein binding defects, rather than for Cu-induced heme binding defects, during zebrafish embryogenesis. These findings provide possible clues for human diseases with ATP7A dysfunction and imbalanced Cu homeostasis.http://www.sciencedirect.com/science/article/pii/S2772735123000665AngiogenesisATP7ACu stressHeme bindingIon transportNeurexin family protein binding |
| spellingShingle | You Wu Wenye Liu Lingya Li Zhipeng Tai Jing-Xia Liu Transcriptional profiles in zebrafish atp7a mutants and responses of atp7a mutants to Cu stress Water Biology and Security Angiogenesis ATP7A Cu stress Heme binding Ion transport Neurexin family protein binding |
| title | Transcriptional profiles in zebrafish atp7a mutants and responses of atp7a mutants to Cu stress |
| title_full | Transcriptional profiles in zebrafish atp7a mutants and responses of atp7a mutants to Cu stress |
| title_fullStr | Transcriptional profiles in zebrafish atp7a mutants and responses of atp7a mutants to Cu stress |
| title_full_unstemmed | Transcriptional profiles in zebrafish atp7a mutants and responses of atp7a mutants to Cu stress |
| title_short | Transcriptional profiles in zebrafish atp7a mutants and responses of atp7a mutants to Cu stress |
| title_sort | transcriptional profiles in zebrafish atp7a mutants and responses of atp7a mutants to cu stress |
| topic | Angiogenesis ATP7A Cu stress Heme binding Ion transport Neurexin family protein binding |
| url | http://www.sciencedirect.com/science/article/pii/S2772735123000665 |
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