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

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

来源：Cytoskeleton, 2015, 72(6): 257-267.

DOI：10.1002/cm.21230

• proteomic
• myofibroblast
• TGF
• actin isoforms

alpha-Smooth Muscle Actin (-SMA), a widely characterized cytoskeletal protein, represents the hallmark of myofibroblast differentiation. Transforming growth factor1 (TGF1) stimulates alpha-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 alpha-SMA is stably incorporated into stress fibers in human myofibroblasts following exposure to TGF1. The unique N-terminal sequence AcEEED, which is critical for -SMA incorporation into stress fibers, was used to screen for AcEEED binding proteins. Tropomyosins were identified as candidate binding proteins. We find that after TGF1 treatment elevated levels of the Tpm1.6/7 isoforms, and to a lesser extent Tpm2.1, precede the increase in alpha-SMA. RNA interference experiments demonstrate that alpha-SMA fails to stably incorporate into stress fibers of TGF1 treated fibroblasts depleted of Tpm1.6/7, but not other tropomyosins. This does not appear to be due to exclusive interactions between alpha-SMA and just the Tpm1.6/7 isoforms. We propose that an additional AcEEED binding factor may be required to generate alpha-SMA filaments containing just Tpm1.6/7 which result in stable incorporation of the resulting filaments into stress fibers.

• 出版日期2015-6