Velez-Aguilera, G., de Dios Gomez-Lopez, J., Jimenez-Gutierrez, G.E. et al. (5 more authors) (2018) Control of nuclear beta-dystroglycan content is crucial for the maintenance of nuclear envelope integrity and function. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1865 (2). pp. 406-420. ISSN 0167-4889
Abstract
β-Dystroglycan (β-DG) is a plasma membrane protein that has ability to target to the nuclear envelope (NE) to maintain nuclear architecture. Nevertheless, mechanisms controlling β-DG nuclear localization and the physiological consequences of a failure of trafficking are largely unknown. We show that β-DG has a nuclear export pathway in myoblasts that depends on the recognition of a nuclear export signal located in its transmembrane domain, by CRM1. Remarkably, NES mutations forced β-DG nuclear accumulation resulting in mislocalization and decreased levels of emerin and lamin B1 and disruption of various nuclear processes in which emerin (centrosome-nucleus linkage and β-catenin transcriptional activity) and lamin B1 (cell cycle progression and nucleoli structure) are critically involved. In addition to nuclear export, the lifespan of nuclear β-DG is restricted by its nuclear proteasomal degradation. Collectively our data show that control of nuclear β-DG content by the combination of CRM1 nuclear export and nuclear proteasome pathways is physiologically relevant to preserve proper NE structure and activity.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2018 Elsevier. This is an author produced version of a paper subsequently published in Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. Uploaded in accordance with the publisher's self-archiving policy. Article available under the terms of the CC-BY-NC-ND licence (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
Keywords: | beta-Dystroglycan; Exportin CRM1; Nuclear export; Nuclear envelope; Proteasome degradation |
Dates: |
|
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: | 09 May 2018 14:45 |
Last Modified: | 21 Nov 2018 01:39 |
Published Version: | https://doi.org/10.1016/j.bbamcr.2017.11.013 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.bbamcr.2017.11.013 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:130548 |