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Article: Using Xenopus tissue cultures for the study of myasthenia gravis pathogenesis

TitleUsing Xenopus tissue cultures for the study of myasthenia gravis pathogenesis
Authors
KeywordsCell-based assay
ADF/cofilin
Xenopus
Neuromuscular junction
Myasthenia gravis
Acetylcholine receptor
Issue Date2014
Citation
Developmental Biology, 2014 How to Cite?
Abstract© 2015 Elsevier Inc. Myasthenia gravis (MG), the most common autoimmune disease of neuromuscular junction (NMJ), is heterogeneous in terms of pathophysiology, which is determined by the pathogenic antigen of autoantibodies targeting to synaptic proteins at the NMJs. Currently, patients suspected with MG are routinely screened for the presence of autoantibodies against acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) using a cell-based assay (CBA) that involves the expression of target synaptic membrane protein in heterologous cell lines. However, some autoantibodies may only show reactivity for binding to densely clustered AChR in the physiological conformation, while AChR clustering is known to involve signaling events orchestrated by over a dozen of postsynaptic proteins. To improve the existing serological diagnosis of MG, this study explored the possibility of using the well-established Xenopus primary culture system as a novel CBA for MG. Here, by examining the pathogenic effects of four MG human plasma samples, we found that the samples from both seropositive and seronegative MG patients effectively induced the disassembly of aneural AChR clusters in cultured Xenopus muscle cells, as well as the nerve-induced AChR clusters in the nerve-muscle co-cultures. Importantly, the disassembly of AChR clusters was spatio-temporally correlated to the disappearance of actin depolymerizing factor (ADF)/cofilin, an actin regulator involved in AChR trafficking and clustering. Taken together, this study develops a reliable CBA using Xenopus primary cultures for screening the pathogenicity of human MG plasma samples, and providing a platform for investigating the pathogenic mechanisms underlying the endocytic trafficking and degradation of AChRs at NMJs in MG patients.
Persistent Identifierhttp://hdl.handle.net/10722/219891
ISSN
2015 Impact Factor: 3.155
2015 SCImago Journal Rankings: 2.554

 

DC FieldValueLanguage
dc.contributor.authorYeo, Hwee Li-
dc.contributor.authorLim, Jorain Yu Ni-
dc.contributor.authorFukami, Yuki-
dc.contributor.authorYuki, Nobuhiro-
dc.contributor.authorLee, Chi Wai-
dc.date.accessioned2015-09-24T04:44:17Z-
dc.date.available2015-09-24T04:44:17Z-
dc.date.issued2014-
dc.identifier.citationDevelopmental Biology, 2014-
dc.identifier.issn0012-1606-
dc.identifier.urihttp://hdl.handle.net/10722/219891-
dc.description.abstract© 2015 Elsevier Inc. Myasthenia gravis (MG), the most common autoimmune disease of neuromuscular junction (NMJ), is heterogeneous in terms of pathophysiology, which is determined by the pathogenic antigen of autoantibodies targeting to synaptic proteins at the NMJs. Currently, patients suspected with MG are routinely screened for the presence of autoantibodies against acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) using a cell-based assay (CBA) that involves the expression of target synaptic membrane protein in heterologous cell lines. However, some autoantibodies may only show reactivity for binding to densely clustered AChR in the physiological conformation, while AChR clustering is known to involve signaling events orchestrated by over a dozen of postsynaptic proteins. To improve the existing serological diagnosis of MG, this study explored the possibility of using the well-established Xenopus primary culture system as a novel CBA for MG. Here, by examining the pathogenic effects of four MG human plasma samples, we found that the samples from both seropositive and seronegative MG patients effectively induced the disassembly of aneural AChR clusters in cultured Xenopus muscle cells, as well as the nerve-induced AChR clusters in the nerve-muscle co-cultures. Importantly, the disassembly of AChR clusters was spatio-temporally correlated to the disappearance of actin depolymerizing factor (ADF)/cofilin, an actin regulator involved in AChR trafficking and clustering. Taken together, this study develops a reliable CBA using Xenopus primary cultures for screening the pathogenicity of human MG plasma samples, and providing a platform for investigating the pathogenic mechanisms underlying the endocytic trafficking and degradation of AChRs at NMJs in MG patients.-
dc.languageeng-
dc.relation.ispartofDevelopmental Biology-
dc.subjectCell-based assay-
dc.subjectADF/cofilin-
dc.subjectXenopus-
dc.subjectNeuromuscular junction-
dc.subjectMyasthenia gravis-
dc.subjectAcetylcholine receptor-
dc.titleUsing Xenopus tissue cultures for the study of myasthenia gravis pathogenesis-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.ydbio.2015.02.017-
dc.identifier.scopuseid_2-s2.0-84924706563-
dc.identifier.eissn1095-564X-

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