Stable incorporation of α-smooth muscle actin into stress fibers is dependent on specific tropomyosin isoforms

Marco Prunotto, Maurizio Bruschi, Peter Gunning, Giulio Gabbiani, Franziska Weibel, Gian Marco Ghiggeri, Andrea Petretto, Andrea Scaloni, Teresa Bonello, Galina Schevzov, Irina Alieva, Marie Luce Bochaton-Piallat, Giovanni Candiano, Vera Dugina, Christine Chaponnier

Research output: Contribution to journalArticle

Abstract

α-Smooth Muscle Actin (α-SMA), a widely characterized cytoskeletal protein, represents the hallmark of myofibroblast differentiation. Transforming growth factorβ1 (TGFβ1) stimulates α-SMA expression and incorporation into stress fibers, thus providing an increased myofibroblast contractile force that participates in tissue remodeling. We have addressed the molecular mechanism by which α-SMA is stably incorporated into stress fibers in human myofibroblasts following exposure to TGFβ1. The unique N-terminal sequence AcEEED, which is critical for α-SMA incorporation into stress fibers, was used to screen for AcEEED binding proteins. Tropomyosins were identified as candidate binding proteins. We find that after TGFβ1 treatment elevated levels of the Tpm1.6/7 isoforms, and to a lesser extent Tpm2.1, precede the increase in α-SMA. RNA interference experiments demonstrate that α-SMA fails to stably incorporate into stress fibers of TGFβ1 treated fibroblasts depleted of Tpm1.6/7, but not other tropomyosins. This does not appear to be due to exclusive interactions between α-SMA and just the Tpm1.6/7 isoforms. We propose that an additional AcEEED binding factor may be required to generate α-SMA filaments containing just Tpm1.6/7 which result in stable incorporation of the resulting filaments into stress fibers.

Original languageEnglish
Pages (from-to)257-267
Number of pages11
JournalCytoskeleton
Volume72
Issue number6
DOIs
Publication statusPublished - Jun 1 2015

Keywords

  • Actin isoforms
  • Myofibroblast
  • Proteomic
  • TGFβ

ASJC Scopus subject areas

  • Cell Biology
  • Structural Biology

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    Prunotto, M., Bruschi, M., Gunning, P., Gabbiani, G., Weibel, F., Ghiggeri, G. M., Petretto, A., Scaloni, A., Bonello, T., Schevzov, G., Alieva, I., Bochaton-Piallat, M. L., Candiano, G., Dugina, V., & Chaponnier, C. (2015). Stable incorporation of α-smooth muscle actin into stress fibers is dependent on specific tropomyosin isoforms. Cytoskeleton, 72(6), 257-267. https://doi.org/10.1002/cm.21230