Characterization of an importin in α/β-recognized nuclear localization signal in β-dystroglycan

Bárbara Lara-Chacón, Mario Bermúdez De León, Daniel Leocadio, Pablo Gómez, Lizeth Fuentes-Mera, Ivette Martínez-Vieyra, Arturo Ortega, David A. Jans, Bulmaro Cisneros

Resultado de la investigación

18 Citas (Scopus)

Resumen

β-dystroglycan (β-DG) is a widely expressed transmembrane protein that plays important roles in connecting the extracellular matrix to the cytoskeleton, and thereby contributing to plasma membrane integrity and signal transduction. We previously observed nuclear localization of β-DG in cultured cell lines, implying the existence of a nuclear targeting mechanism that directs it to the nucleus instead of the plasma membrane. In this study, we delineate the nuclear import pathway of β-DG, characterizing a functional nuclear localization signal (NLS) in the β-DG cytoplasmic domain, within amino acids 776-782. The NLS either alone or in the context of the whole β-DG protein was able to target the heterologous GFP protein to the nucleus, with site-directed mutagenesis indicating that amino acids R779and K780are critical for NLS functionality. The nuclear transport molecules Importin (Imp)α and Impβ bound with high affinity to the NLS of β-DG and were found to be essential for NLS-dependent nuclear import in an in vitro reconstituted nuclear transport assay; cotransfection experiments confirmed the dependence on Ran for nuclear accumulation. Intriguingly, experiments suggested that tyrosine phosphorylation of β-DG may result in cytoplasmic retention, with Y892playing a key role. β-DG thus follows a conventional Impα/β-dependent nuclear import pathway, with important implications for its potential function in the nucleus. © 2010 Wiley-Liss, Inc.
Idioma originalEnglish
Páginas (desde-hasta)706-717
Número de páginas12
PublicaciónJournal of Cellular Biochemistry
DOI
EstadoPublished - 1 jun 2010
Publicado de forma externa

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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