Stable incorporation of α-smooth muscle actin into stress fibers is dependent on specific tropomyosin isoforms.
Cytoskeleton (Hoboken)
; 72(6): 257-67, 2015 Jun.
Article
en En
| MEDLINE
| ID: mdl-26147585
ABSTRACT
α-Smooth Muscle Actin (α-SMA), a widely characterized cytoskeletal protein, represents the hallmark of myofibroblast differentiation. Transforming growth factorß1 (TGFß1) 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 TGFß1. 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 TGFß1 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 TGFß1 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tropomiosina
/
Isoformas de Proteínas
/
Miofibroblastos
/
Fibroblastos
/
Músculo Liso
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cytoskeleton (Hoboken)
Año:
2015
Tipo del documento:
Article
País de afiliación:
Suiza