A role for beta-dystroglycan in the organization and structure of the nucleus in myoblasts

作者：Martinez Vieyra Ivette A; Vasquez Limeta Alejandra; Gonzalez Ramirez Ricardo; Morales Lazaro Sara L; Mondragon Monica; Mondragon Ricardo; Ortega Arturo; Winder Steve J; Cisneros Bulmaro^*

来源：Biochimica et Biophysica Acta-Molecular Cell Research, 2013, 1833(3): 698-711.

DOI：10.1016/j.bbamcr.2012.11.019

• Dystroglycan
• Emerin
• Nuclear lamins
• Nuclear envelope
• Nucleoli

We recently characterized a nuclear import pathway for beta-dystroglycan; however, its nuclear role remains unknown. In this study, we demonstrate for the first time, the interaction of beta-dystroglycan with distinct proteins from different nuclear compartments, including the nuclear envelope (NE) (emerin and lamins A/C and B1), splicing speckles (SC35), Cajal bodies (p80-coilin), and nucleoli (Nopp140). Electron microscopy analysis revealed that beta-dystroglycan localized in the inner nuclear membrane, nucleoplasm, and nucleoli. Interestingly, downregulation of beta-dystroglycan resulted in both mislocalization and decreased expression of emerin and lamin B1, but not lamin A/C, as well in disorganization of nucleoli, Cajal bodies, and splicing speckles with the concomitant decrease in the levels of Nopp140, and p80-coilin, but not SC35. Quantitative reverse transcription PCR and cycloheximide-mediated protein arrest assays revealed that beta-dystroglycan deficiency did not change mRNA expression of NE proteins emerin and lamin B1 bud did alter their stability, accelerating protein turnover. Furthermore, knockdown of beta-dystroglycan disrupted NE-mediated processes including nuclear morphology and centrosome-nucleus linkage, which provides evidence that beta-dystroglycan association with NE proteins is biologically relevant. Unexpectedly, beta-dystroglycan-depleted cells exhibited multiple centrosomes, a characteristic of cancerous cells. Overall, these findings imply that beta-dystroglycan is a nuclear scaffolding protein involved in nuclear organization and NE structure and function, and that might be a contributor to the biogenesis of nuclear envelopathies.

• 出版日期2013-3