TY - JOUR
T1 - The molecular basis and biologic significance of the β-dystroglycan-emerin interaction
AU - Gómez-Monsivais, Wendy Lilián
AU - Monterrubio-Ledezma, Feliciano
AU - Huerta-Cantillo, Jazmin
AU - Mondragon-Gonzalez, Ricardo
AU - Alamillo-Iniesta, Alma
AU - García-Aguirre, Ian
AU - Azuara-Medina, Paulina Margarita
AU - Arguello-García, Raúl
AU - Rivera-Monroy, Jhon Erick
AU - Holaska, James M.
AU - Hernández-Méndez, Jesús Mauricio Ernesto
AU - Garrido, Efraín
AU - Magaña, Jonathan Javier
AU - Winder, Steve J.
AU - Brancaccio, Andrea
AU - Martínez-Vieyra, Ivette
AU - Navarro-Garcia, Fernando
AU - Cisneros, Bulmaro
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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.
AB - 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.
KW - Emerin
KW - Emery-Dreifuss muscular dystrophy
KW - Nuclear envelope
KW - Proteasome
KW - Surface plasmon resonance assay
KW - β-dystroglycan
UR - http://www.scopus.com/inward/record.url?scp=85089796038&partnerID=8YFLogxK
U2 - 10.3390/ijms21175944
DO - 10.3390/ijms21175944
M3 - Artículo
C2 - 32824881
AN - SCOPUS:85089796038
SN - 1661-6596
VL - 21
SP - 1
EP - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 17
M1 - 5944
ER -