Title
The molecular basis and biologic significance of the β-dystroglycan-emerin interaction
DOI
https://doi.org/10.3390/ijms21175944
Document Type
Article
Publication Date
9-1-2020
Publication Title
International Journal of Molecular Sciences
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.
Volume
21
Issue
17
First Page
1
Last Page
20
ISSN
16616596
Recommended Citation
Gómez-Monsivais, Wendy Lilián; Monterrubio-Ledezma, Feliciano; Huerta-Cantillo, Jazmin; Mondragon-Gonzalez, Ricardo; Alamillo-Iniesta, Alma; García-Aguirre, Ian; Azuara-Medina, Paulina Margarita; Arguello-García, Raúl; Rivera-Monroy, Jhon Erick; Holaska, James M.; Hernández-Méndez, Jesús Mauricio Ernesto; Garrido, Efraín; Magaña, Jonathan Javier; Winder, Steve J.; Brancaccio, Andrea; Martínez-Vieyra, Ivette; Navarro-Garcia, Fernando; and Cisneros, Bulmaro, "The molecular basis and biologic significance of the β-dystroglycan-emerin interaction" (2020). Scopus Unisalle. 62.
https://ciencia.lasalle.edu.co/scopus_unisalle/62
PubMed ID
32824881
Identifier
SCOPUS_ID:85089796038