Table 2.
Actin Dynamics in Mechanosensing Downstream from the Focal Adhesion.
| The role of actin in mechanotransduction | ||
|---|---|---|
| Normal role in fibroblast physiology | Age-related changes | |
| Actin as part of the cytoskeleton | In mechanosensing, the actin cytoskeleton rearranges in response to ECM tension (Grabec et al., 2000) and takes part in fibroblast-myofibroblast differentiation (Omelchenko et al., 2002). | Aging is associated with drastic biochemical changes that may alter actin polymerization and expression (Cieslik et al., 2011; Lai and Wong, 2020). Oxidative stress can alter actin turnover and/or filament organization, due to ROS or methionine sulfoxidation imbalance (Aberle, 2013; Varland et al., 2019). |
| The impact of oxidative stress in actin polymerization has been demonstrated in eukaryotic cells (Farah et al., 2011) and adult cardiomyocytes (Angelini et al., 2020) but has not been shown in cardiac fibroblasts. | ||
| Actin in fibroblast maturation | During their maturation, myofibroblasts express a-SMA, a contractile actin isoform, in their cytoskeleton (Hinz et al., 2001, 2003); this favors wound healing (Hinz, 2006; Santiago et al., 2010). | Aged cardiac fibroblasts show decreased a-SMA isoform, along with a decreased and disorganized F-actin network leading to impaired cardiac fibroblast contractility (Cieslik et al., 2011). |
| Actin and mRNA “zip-coding” | The fibroblast is the only cell type in which mRNA zip-coding (cytoplasmic sorting of mRNA) persists after embryogenesis (Jansen, 2001; Lopez de Heredia and Jansen, 2004). | Modulation of mRNA turnover by age-related factors (Borbolis and Syntichaki, 2015) could potentially impair mRNA zip-coding. Its role remains unknown in the aging heart. |
| β-actin mRNA is reported to be extensively zip-coded and enriched at the FA site (Bassell et al., 1998). | ||
| Integrin signaling promotes ZBP phosphorylation, and therefore mRNA zipcoding in fibroblasts (Bassell et al., 1998; Chicurel et al., 1998; Kislauskis et al., 1994; Shestakova et al., 2001). | ||
| F-actin binds ZBP-1 and ensures the zip-coded mRNAs localization through polymerization (Nicastro et al., 2017). | ||