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

Gómez-Monsivais, Wendy Lilián; Monterrubio-Ledezma, Feliciano; Huerta-Cantillo, Jazmín; Mondragón-González, Ricardo; Alamillo-Iniesta, Alma; García‐Aguirre, Ian; Azuara-Medina, Paulina Margarita; Argüello-García, Raúl; Rivera‐Monroy, Jhon; Holaska, James M.; Hernández-Méndez, Jesús Mauricio Ernesto; Garrido, Efraín; Magaña, Jonathan J.; Winder, Steve J.; Brancaccio, Andrea; Martínez‐Vieyra, Ivette; Cisneros, Bulmaro

doi:10.3390/ijms21175944

Cited by 5 publications

(3 citation statements)

References 41 publications

(54 reference statements)

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“…However, the function and consequences of this nuclear translocation are not yet known. It has been demonstrated that β-DG contributes to the stability of the nuclear membrane in murine myoblasts ( Gómez-Monsivais et al, 2020 ), but it has also been highlighted that the translocation of β-DG fragments into the nucleus is associated with alterations in the expression levels of some genes in prostate cancer cells ( Mathew et al, 2013 ). It remains to be clarified if and how nuclear β-DG exerts control over gene expression and whether this is the consequence of an activation of a regulated cascade of signals leading from the external stimuli to the cell response.…”

Section: Dg and Signal Transductionmentioning

confidence: 99%

From adhesion complex to signaling hub: the dual role of dystroglycan

Sciandra,

Bozzi,

Bigotti

2023

Front. Mol. Biosci.

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Dystroglycan (DG) is a transmembrane protein widely expressed in multiple cells and tissues. It is formed by two subunits, α− and β-DG, and represents a molecular bridge between the outside and the inside of the cell, which is essential for the mechanical and structural stability of the plasma membrane. The α-subunit is a cell-surface protein that binds to the extracellular matrix (ECM) and is tightly associated with the plasma membrane via a non-covalent interaction with the β-subunit, which, in turn, is a transmembrane protein that binds to the cytoskeletal actin. DG is a versatile molecule acting not only as a mechanical building block but also as a modulator of outside–inside signaling events. The cytoplasmic domain of β-DG interacts with different adaptor and cytoskeletal proteins that function as molecular switches for the transmission of ECM signals inside the cells. These interactions can modulate the involvement of DG in different biological processes, ranging from cell growth and survival to differentiation and proliferation/regeneration. Although the molecular events that characterize signaling through the ECM-DG-cytoskeleton axis are still largely unknown, in recent years, a growing list of evidence has started to fill the gaps in our understanding of the role of DG in signal transduction. This mini-review represents an update of recent developments, uncovering the dual role of DG as an adhesion and signaling molecule that might inspire new ideas for the design of novel therapeutic strategies for pathologies such as muscular dystrophy, cardiomyopathy, and cancer, where the DG signaling hub plays important roles.

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Section: Dg and Signal Transductionmentioning

confidence: 99%

From adhesion complex to signaling hub: the dual role of dystroglycan

Sciandra,

Bozzi,

Bigotti

2023

Front. Mol. Biosci.

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“…Interestingly, however, the determined localisation of the truncated βDG constructs in this study was not unprecedented. The expression of full-length βDG has been used extensively to study nuclear functions and is routinely observed in an ER-like distribution [ 4 , 11 , 26 , 42 , 43 ]. Confocal analysis of C2C12 myoblasts expressing full-length βDG also indicates its presence throughout the nucleus, though how it escapes the membranous environment is unclear [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

The Role of β-Dystroglycan in Nuclear Dynamics

Cook,

Stevenson,

Jacobs

et al. 2024

Cells

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Dystroglycan is a ubiquitously expressed heterodimeric cell-surface laminin receptor with roles in cell adhesion, signalling, and membrane stabilisation. More recently, the transmembrane β-subunit of dystroglycan has been shown to localise to both the nuclear envelope and the nucleoplasm. This has led to the hypothesis that dystroglycan may have a structural role at the nuclear envelope analogous to its role at the plasma membrane. The biochemical fraction of myoblast cells clearly supports the presence of dystroglycan in the nucleus. Deletion of the dystroglycan protein by disruption of the DAG1 locus using CRISPR/Cas9 leads to changes in nuclear size but not overall morphology; moreover, the Young’s modulus of dystroglycan-deleted nuclei, as determined by atomic force microscopy, is unaltered. Dystroglycan-disrupted myoblasts are also no more susceptible to nuclear stresses including chemical and mechanical, than normal myoblasts. Re-expression of dystroglycan in DAG1-disrupted myoblasts restores nuclear size without affecting other nuclear parameters.

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“…EMD binds to β-catenin, forming a protein complex which in the presence of EMD loss or malfunction may alter the β-catenin cycle and thus activate the transcription of genes implicated in cell hypertrophy and probably signaling pathways involved in overlap with DCM. β-Catenin is a component of the intercalated discs of the cardiomyocyte, and its alteration modifies the intercellular junctions; it has been suggested that this may be related to atrioventricular conduction disturbances [25,29]. These findings in mice suggest that therapeutic inhibition of the Wnt/β-catenin complex could afford benefit for patients with EDMD [30].…”

Section: Molecular Hypothesismentioning

confidence: 99%

Natural History of Dilated Cardiomyopathy Due to c.77T>C (p.Val26Ala) in Emerin Protein

Báez-Ferrer,

Díaz-Flores-Estévez,

Pérez-Cejas

et al. 2024

JCM

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(1) Introduction: Dilated cardiomyopathy (DCM) mainly affects young individuals and is the main indication of heart transplantation. The variant c.77T>C (p.Val26Ala) of the gene coding for emerin (EMD) in chromosome Xq28 has been catalogued as a pathogenic variant for the development of DCM, exhibiting an X-linked inheritance pattern. (2) Methods: A retrospective study was conducted covering the period 2015–2023 in patients with DCM of genetic origin. The primary endpoint was patient age at onset of the first composite major cardiac event, in the form of a first episode of heart failure, malignant ventricular arrhythmia, or end-stage heart failure, according to the presence of truncating variant in titin gene (TTNtv) versus the p.Val26Ala mutation in the EMD protein. (3) Results: A total of 31 and 22 patients were included in the EMD group and TTNtv group, respectively. The primary endpoint was significantly higher in the EMD group, with a hazard ratio of 4.16 (95% confidence interval: 1.83–9.46; p = 0.001). At 55 years of age, all the patients in the EMD group had already presented heart failure, nine presented malignant ventricular arrhythmia (29%), and 13 required heart transplantation (42%). (4) Conclusions: DCM secondary to the c.77T>C (p.Val26Ala) mutation in the EMD gene is associated to an increased risk of major cardiac events compared to patients with DCM due to TTNtv, with a large proportion of transplanted patients in the fifth decade of life.

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

Cited by 5 publications

References 41 publications

From adhesion complex to signaling hub: the dual role of dystroglycan

From adhesion complex to signaling hub: the dual role of dystroglycan

The Role of β-Dystroglycan in Nuclear Dynamics

Natural History of Dilated Cardiomyopathy Due to c.77T>C (p.Val26Ala) in Emerin Protein

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