The Molecular Basis and Biologic Significance of the β-Dystroglycan-Emerin Interaction

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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Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2020-08-01
Series:International Journal of Molecular Sciences
Subjects:
β-dystroglycan
emerin
nuclear envelope
Emery-Dreifuss muscular dystrophy
surface plasmon resonance assay
proteasome
Online Access:https://www.mdpi.com/1422-0067/21/17/5944
Description
Summary: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.
ISSN:1661-6596
1422-0067

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