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Metavinculin Tunes the Flexibility and the Architecture of Vinculin-Induced Bundles of Actin Filaments.
Oztug Durer, Zeynep A; McGillivary, Rebecca M; Kang, Hyeran; Elam, W Austin; Vizcarra, Christina L; Hanein, Dorit; De La Cruz, Enrique M; Reisler, Emil; Quinlan, Margot E.
Afiliación
  • Oztug Durer ZA; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095-1569, USA.
  • McGillivary RM; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095-1569, USA.
  • Kang H; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.
  • Elam WA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.
  • Vizcarra CL; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095-1569, USA.
  • Hanein D; Bioinformatics and Structural Biology Program, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
  • De La Cruz EM; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.
  • Reisler E; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095-1569, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095-1570, USA.
  • Quinlan ME; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095-1569, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095-1570, USA. Electronic address: margot@chem.ucla.edu.
J Mol Biol ; 427(17): 2782-98, 2015 Aug 28.
Article en En | MEDLINE | ID: mdl-26168869
Vinculin is an abundant protein found at cell-cell and cell-extracellular matrix junctions. In muscles, a longer splice isoform of vinculin, metavinculin, is also expressed. The metavinculin-specific insert is part of the C-terminal tail domain, the actin-binding site of both isoforms. Mutations in the metavinculin-specific insert are linked to heart disease such as dilated cardiomyopathies. Vinculin tail domain (VT) both binds and bundles actin filaments. Metavinculin tail domain (MVT) binds actin filaments in a similar orientation but does not bundle filaments. Recently, MVT was reported to sever actin filaments. In this work, we asked how MVT influences F-actin alone or in combination with VT. Cosedimentation and limited proteolysis experiments indicated a similar actin binding affinity and mode for both VT and MVT. In real-time total internal reflection fluorescence microscopy experiments, MVT's severing activity was negligible. Instead, we found that MVT binding caused a 2-fold reduction in F-actin's bending persistence length and increased susceptibility to breakage. Using mutagenesis and site-directed labeling with fluorescence probes, we determined that MVT alters actin interprotomer contacts and dynamics, which presumably reflect the observed changes in bending persistence length. Finally, we found that MVT decreases the density and thickness of actin filament bundles generated by VT. Altogether, our data suggest that MVT alters actin filament flexibility and tunes filament organization in the presence of VT. Both of these activities are potentially important for muscle cell function. Perhaps MVT allows the load of muscle contraction to act as a signal to reorganize actin filaments.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Citoesqueleto de Actina / Actinas / Vinculina / Músculo Esquelético / Factores Despolimerizantes de la Actina / Contracción Muscular Límite: Animals / Humans Idioma: En Revista: J Mol Biol Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Citoesqueleto de Actina / Actinas / Vinculina / Músculo Esquelético / Factores Despolimerizantes de la Actina / Contracción Muscular Límite: Animals / Humans Idioma: En Revista: J Mol Biol Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos