Gómez-Monsivais, W.L., Monterrubio-Ledezma, F., Huerta-Cantillo, J. et al. (15 more authors) (2020) The molecular basis and biologic significance of the β-dystroglycan-emerin interaction. International Journal of Molecular Sciences, 21 (17). 5944.
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | Emery-Dreifuss muscular dystrophy; emerin; nuclear envelope; proteasome; surface plasmon resonance assay; β-dystroglycan |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 08 Sep 2020 13:25 |
Last Modified: | 08 Sep 2020 13:25 |
Status: | Published |
Publisher: | MDPI AG |
Refereed: | Yes |
Identification Number: | 10.3390/ijms21175944 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:165033 |