title: A role for β-dystroglycan in the organization and structure of the nucleus in myoblasts.
abstract: We recently characterized a nuclear import pathway for β-dystroglycan; however, its nuclear role remains unknown. In this study, we demonstrate for the first time, the interaction of β-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 β-dystroglycan localized in the inner nuclear membrane, nucleoplasm, and nucleoli. Interestingly, downregulation of β-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 β-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 β-dystroglycan disrupted NE-mediated processes including nuclear morphology and centrosome-nucleus linkage, which provides evidence that β-dystroglycan association with NE proteins is biologically relevant. Unexpectedly, β-dystroglycan-depleted cells exhibited multiple centrosomes, a characteristic of cancerous cells. Overall, these findings imply that β-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.
authors.affiliation: Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del IPN, México, DF 07360, Mexico.
authors.forename: Ivette A
authors.initials: IA
authors.lastname: Martínez-Vieyra
authors.forename: Alejandra
authors.initials: A
authors.lastname: Vásquez-Limeta
authors.forename: Ricardo
authors.initials: R
authors.lastname: González-Ramírez
authors.forename: Sara L
authors.initials: SL
authors.lastname: Morales-Lázaro
authors.forename: Mónica
authors.initials: M
authors.lastname: Mondragón
authors.forename: Ricardo
authors.initials: R
authors.lastname: Mondragón
authors.forename: Arturo
authors.initials: A
authors.lastname: Ortega
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Winder
authors.forename: Bulmaro
authors.initials: B
authors.lastname: Cisneros
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure*; D002478:Cells, Cultured; D020541:Coiled Bodies / Q000235:genetics / Q000378:metabolism*; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D047468:Immunoprecipitation; D034921:Lamin Type B / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D034921:Lamin Type B; D008565:Membrane Proteins; C513068:Nolc1 protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C092710:emerin; C068921:p80-coilin; D049030:Dystroglycans