Nuclear F-actin Formation and Reorganization upon Cell Spreading

Abstract

Background: Nuclear actin dynamics may function during basic cellular processes such as adhesion, differentiation, cell shape, and motility. Results: Integrin signaling induces nuclear actin polymerization via the LINC complex in response to fibronectin stimulation or cell spreading. Conclusion: Nuclear actin reorganization occurs during cell spreading and fibronectin stimulation. Significance: This may have important implications for understanding mechanotransduction and nuclear plasticity for matrixdirected differentiation.

Integrins synergise to induce expression of the MRTF-A–SRF target gene ISG15 for promoting cancer cell invasion

“…They regulate the activity of small GTPases, actin binding, bundling and modifying proteins to enable cytoskeletal dynamics, membrane protrusions and invadopodia formation (Bishop and Hall, 2000;Hall, 2012;Hoshino et al, 2013;Murphy and Courtneidge, 2011). Interestingly, a recent paper showed that integrins also regulate the nuclear translocation of MRTF-A and induce MRTF-A-SRF target gene expression (Plessner et al, 2015). Because tumour cells express different types of integrins, it is unclear whether and how they co-operate to achieve maximal efficiency in tissue invasion and migration.…”

“…Integrin-dependent regulation of gene expression is primarily thought to arise from cross talk with growth factor receptors that increase the activity of mitogenactivated protein (MAP) kinase pathways. A recent study, however, reported that integrins can also control gene transcription by releasing the association of the transcriptional co-activator myocardin-related transcription factor-A (MRTF-A, also known as MKL1 or MAL) from monomeric or globular (G-) actin (Miralles et al, 2003;Plessner et al, 2015). MRTF-A belongs to the myocardin-related family of transcriptional co-activators, which consists of myocardin, MRTF-A and MRTF-B (also known as MKL2).…”

Nuclear α-catenin mediates the DNA damage response via β-catenin and nuclear actin

“…Polymerizing nuclear actin may act as a scaffold for other repair proteins at sites of DNA damage (Andrin et al, 2012), locally alter nuclear actin dynamics leading to downstream changes in transcription and chromatin remodeling (de Lanerolle and Serebryannyy, 2011;Serebryannyy et al, 2016a,b), or tether repair factories to the nuclear matrix and other nuclear subcompartments (Koehler and Hanawalt, 1996;Mahen et al, 2013;Marnef and Legube, 2017). Notably, lamins are known to regulate genomic stability as well as DNA damage repair (Gonzalo, 2014) and have been shown to interact with nuclear actin (Ho et al, 2013;Plessner et al, 2015;Simon et al, 2010). Multiple studies have identified other actin regulatory proteins that are able to translocate into the nucleus and are involved in the DNA response including JMY (Lin et al, 2014;Zuchero et al, 2009), filamin A (Yue et al, 2013), Arp5 (Kitayama et al, 2009), APC (Kouzmenko et al, 2008;Meniel et al, 2015;Narayan and Sharma, 2015), formin-2, spire-1/2 (Belin et al, 2015), myosin VI (Jung et al, 2006) and nuclear histone deacetylases (HDACs; Serebryannyy et al, 2016a), as well as p53, which is speculated to directly bind F-actin (Metcalfe et al, 1999).…”

Atomic force microscopy studies on cellular elastic and viscoelastic properties

“…In addition, during mitotic rounding, the actin cytoskeleton is completely remodeled to generate a rigid and rounded actomyosin cortex and cell-substrate adhesion is lost (Matthews et al, 2012). Actin cytoskeleton is one of the most abundant proteins in the cytosol of mammalian cells (Plessner et al, 2015). Hence, the changes of actin cytoskeleton may lead to changes in cellular morphology as well as in cellular elastic and viscoelastic properties.…”