The Molecular Basis and Biologic Significance of the β-Dystroglycan-Emerin Interaction
β-dystroglycan (β-DG) assembles with lamins A/C and B1 and emerin at the nuclear envelope (NE) to maintain proper nuclear architecture and function. To provide insight into the nuclear function of β-DG, we characterized the interaction between β-DG and emerin at the molecular level. Emerin is a majo...
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MDPI AG
2020-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/17/5944 |
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| author | Wendy Lilián Gómez-Monsivais Feliciano Monterrubio-Ledezma Jazmin Huerta-Cantillo Ricardo Mondragon-Gonzalez Alma Alamillo-Iniesta Ian García-Aguirre Paulina Margarita Azuara-Medina Raúl Arguello-García Jhon Erick Rivera-Monroy James M. Holaska Jesús Mauricio Ernesto Hernández-Méndez Efraín Garrido Jonathan Javier Magaña Steve J. Winder Andrea Brancaccio Ivette Martínez-Vieyra Fernando Navarro-Garcia Bulmaro Cisneros |
| author_facet | Wendy Lilián Gómez-Monsivais Feliciano Monterrubio-Ledezma Jazmin Huerta-Cantillo Ricardo Mondragon-Gonzalez Alma Alamillo-Iniesta Ian García-Aguirre Paulina Margarita Azuara-Medina Raúl Arguello-García Jhon Erick Rivera-Monroy James M. Holaska Jesús Mauricio Ernesto Hernández-Méndez Efraín Garrido Jonathan Javier Magaña Steve J. Winder Andrea Brancaccio Ivette Martínez-Vieyra Fernando Navarro-Garcia Bulmaro Cisneros |
| author_sort | Wendy Lilián Gómez-Monsivais |
| collection | DOAJ |
| description | β-dystroglycan (β-DG) assembles with lamins A/C and B1 and emerin at the nuclear envelope (NE) to maintain proper nuclear architecture and function. To provide insight into the nuclear function of β-DG, we characterized the interaction between β-DG and emerin at the molecular level. Emerin is a major NE protein that regulates multiple nuclear processes and whose deficiency results in Emery–Dreifuss muscular dystrophy (EDMD). Using truncated variants of β-DG and emerin, via a series of in vitro and in vivo binding experiments and a tailored computational analysis, we determined that the β-DG–emerin interaction is mediated at least in part by their respective transmembrane domains (TM). Using surface plasmon resonance assays we showed that emerin binds to β-DG with high affinity (KD in the nanomolar range). Remarkably, the analysis of cells in which DG was knocked out demonstrated that loss of β-DG resulted in a decreased emerin stability and impairment of emerin-mediated processes. β-DG and emerin are reciprocally required for their optimal targeting within the NE, as shown by immunofluorescence, western blotting and immunoprecipitation assays using emerin variants with mutations in the TM domain and B-lymphocytes of a patient with EDMD. In summary, we demonstrated that β-DG plays a role as an emerin interacting partner modulating its stability and function. |
| first_indexed | 2024-03-10T17:14:06Z |
| format | Article |
| id | doaj.art-5ce0940605684938aef7149135b6c034 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T17:14:06Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5ce0940605684938aef7149135b6c0342023-11-20T10:34:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012117594410.3390/ijms21175944The Molecular Basis and Biologic Significance of the β-Dystroglycan-Emerin InteractionWendy Lilián Gómez-Monsivais0Feliciano Monterrubio-Ledezma1Jazmin Huerta-Cantillo2Ricardo Mondragon-Gonzalez3Alma Alamillo-Iniesta4Ian García-Aguirre5Paulina Margarita Azuara-Medina6Raúl Arguello-García7Jhon Erick Rivera-Monroy8James M. Holaska9Jesús Mauricio Ernesto Hernández-Méndez10Efraín Garrido11Jonathan Javier Magaña12Steve J. Winder13Andrea Brancaccio14Ivette Martínez-Vieyra15Fernando Navarro-Garcia16Bulmaro Cisneros17Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), 07360 Mexico City, MexicoDepartment of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), 07360 Mexico City, MexicoCell Biology Department, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), 07360 Mexico City, MexicoDepartment of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), 07360 Mexico City, MexicoDepartment of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), 07360 Mexico City, MexicoDepartment of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), 07360 Mexico City, MexicoDepartment of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), 07360 Mexico City, MexicoDepartment of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), 07360 Mexico City, MexicoDepartment of Molecular Biology, Faculty of Medicine, GZMB, Georg-August University, 37073 Göttingen, GermanyDepartment of Biomedical Sciences, Cooper Medical School of Rowan University, 401 S Broadway, Camden, NJ 08028, USADepartment of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), 07360 Mexico City, MexicoDepartment of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), 07360 Mexico City, MexicoLaboratory of Genomic Medicine, Department of Genetics, National Rehabilitation Institute-Luis Guillermo Ibarra Ibarra (INR-LGII), 14389 Mexico City, MexicoDepartment of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UKSchool of Biochemistry, University of Bristol, Bristol BS8 1TD, UKLaboratory of Hematobiology, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, 07320 Ciudad de México, MexicoCell Biology Department, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), 07360 Mexico City, MexicoDepartment of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), 07360 Mexico City, Mexicoβ-dystroglycan (β-DG) assembles with lamins A/C and B1 and emerin at the nuclear envelope (NE) to maintain proper nuclear architecture and function. To provide insight into the nuclear function of β-DG, we characterized the interaction between β-DG and emerin at the molecular level. Emerin is a major NE protein that regulates multiple nuclear processes and whose deficiency results in Emery–Dreifuss muscular dystrophy (EDMD). Using truncated variants of β-DG and emerin, via a series of in vitro and in vivo binding experiments and a tailored computational analysis, we determined that the β-DG–emerin interaction is mediated at least in part by their respective transmembrane domains (TM). Using surface plasmon resonance assays we showed that emerin binds to β-DG with high affinity (KD in the nanomolar range). Remarkably, the analysis of cells in which DG was knocked out demonstrated that loss of β-DG resulted in a decreased emerin stability and impairment of emerin-mediated processes. β-DG and emerin are reciprocally required for their optimal targeting within the NE, as shown by immunofluorescence, western blotting and immunoprecipitation assays using emerin variants with mutations in the TM domain and B-lymphocytes of a patient with EDMD. In summary, we demonstrated that β-DG plays a role as an emerin interacting partner modulating its stability and function.https://www.mdpi.com/1422-0067/21/17/5944β-dystroglycanemerinnuclear envelopeEmery-Dreifuss muscular dystrophysurface plasmon resonance assayproteasome |
| spellingShingle | Wendy Lilián Gómez-Monsivais Feliciano Monterrubio-Ledezma Jazmin Huerta-Cantillo Ricardo Mondragon-Gonzalez Alma Alamillo-Iniesta Ian García-Aguirre Paulina Margarita Azuara-Medina Raúl Arguello-García Jhon Erick Rivera-Monroy James M. Holaska Jesús Mauricio Ernesto Hernández-Méndez Efraín Garrido Jonathan Javier Magaña Steve J. Winder Andrea Brancaccio Ivette Martínez-Vieyra Fernando Navarro-Garcia Bulmaro Cisneros The Molecular Basis and Biologic Significance of the β-Dystroglycan-Emerin Interaction International Journal of Molecular Sciences β-dystroglycan emerin nuclear envelope Emery-Dreifuss muscular dystrophy surface plasmon resonance assay proteasome |
| title | The Molecular Basis and Biologic Significance of the β-Dystroglycan-Emerin Interaction |
| title_full | The Molecular Basis and Biologic Significance of the β-Dystroglycan-Emerin Interaction |
| title_fullStr | The Molecular Basis and Biologic Significance of the β-Dystroglycan-Emerin Interaction |
| title_full_unstemmed | The Molecular Basis and Biologic Significance of the β-Dystroglycan-Emerin Interaction |
| title_short | The Molecular Basis and Biologic Significance of the β-Dystroglycan-Emerin Interaction |
| title_sort | molecular basis and biologic significance of the β dystroglycan emerin interaction |
| topic | β-dystroglycan emerin nuclear envelope Emery-Dreifuss muscular dystrophy surface plasmon resonance assay proteasome |
| url | https://www.mdpi.com/1422-0067/21/17/5944 |
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