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

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• 作者：Ivette A. Martí ; nez-Vieyra^a ; Alejandra V&#225 ; squez-Limeta^a ; Ricardo Gonz&#225 ; lez-Ramí ; rez^b ; Sara L. Morales-L&#225 ; zaro^c ; Mó ; nica Mondragó ; n^d ; Ricardo Mondragó ; n^d ; Arturo Ortega^a ; Steve J. Winder^e ; Bulmaro Cisneros^a ; ^{bcisnero@cinvestav.mx}
• 关键词：NE ; Nuclear envelope ; INM ; Inner nuclear membrane ; ONM ; Outer nuclear membrane
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：2013
• 出版时间：March, 2013
• 年：2013
• 卷：1833
• 期：3
• 页码：698-711
• 全文大小：2032 K

文摘

We recently characterized a nuclear import pathway for ¦Â-dystroglycan; however, its nuclear role remains unknown. In this study, we demonstrate for the first time, the interaction of ¦Â-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 ¦Â-dystroglycan localized in the inner nuclear membrane, nucleoplasm, and nucleoli. Interestingly, downregulation of ¦Â-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 ¦Â-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 ¦Â-dystroglycan disrupted NE-mediated processes including nuclear morphology and centrosome-nucleus linkage, which provides evidence that ¦Â-dystroglycan association with NE proteins is biologically relevant. Unexpectedly, ¦Â-dystroglycan-depleted cells exhibited multiple centrosomes, a characteristic of cancerous cells. Overall, these findings imply that ¦Â-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.