Control of nuclear β-dystroglycan content is crucial for the maintenance of nuclear envelope integrity and function

Publication date: February 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 2 Author(s): Griselda Vélez-Aguilera, Juan de Dios Gómez-López, Guadalupe E. Jiménez-Gutiérrez, Alejandra Vásquez-Limeta, Marco S. Laredo-Cisneros, Pablo Gómez, Steve J. Winder, Bulmaro Cisneros 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.
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research