scholarly journals Lamin A/C Deficiency Enables Increased Myosin2 Bipolar Filament Ensembles Which Promote Divergent Actomyosin Network Anomalies Through Self Organization

2020 ◽  
Author(s):  
O’Neil Wiggan ◽  
Jennifer G. DeLuca ◽  
Timothy J. Stasevich ◽  
James R. Bamburg
Keyword(s):  
Live Cell Imaging ◽  
Serum Response Factor ◽  
Myosin Ii ◽  
Lamin A ◽  
Fiber Assembly ◽  
Cytoplasmic Actomyosin ◽  
Bipolar Filament ◽  
Actin Comet Tails ◽  
Serum Response ◽  
Transcriptional Feedback

AbstractNuclear envelope proteins influence cell cytoarchitecure by poorly understood mechanisms. Here we show that siRNA-mediated silencing of lamin A/C (LMNA) promotes contrasting stress fiber assembly and disassembly in individual cells and within cell populations. We show that LMNA deficient cells have elevated myosin-II bipolar filament accumulations, irregular formation of actin comet tails and podosome-like adhesions, increased steady state nuclear localization of the mechanosensitive transcription factors MKL1 and YAP, and induced expression of some MKL1/Serum Response Factor (SRF) regulated genes such as that encoding myosin-IIA (MYH9). Our studies utilizing live cell imaging and pharmacological inhibition of myosin-II, support a mechanism of deregulated myosin-II self-organizing activity at the nexus of divergent actin cytoskeletal aberrations resultant from LMNA loss. In light of our results, we propose a model of how the nucleus, via linkage to the cytoplasmic actomyosin network, may act to control myosin-II contractile behavior through both mechanical and transcriptional feedback mechanisms.

scholarly journals Lamin A/C deficiency enables increased myosin-II bipolar filament ensembles that promote divergent actomyosin network anomalies through self-organization

2020 ◽  
Vol 31 (21) ◽  
pp. 2363-2378
Author(s):  
O’Neil Wiggan ◽  
Jennifer G. DeLuca ◽  
Timothy J. Stasevich ◽  
James R. Bamburg
Keyword(s):  
Myosin Ii ◽  
Nuclear Lamina ◽  
Self Organization ◽  
Lamin A ◽  
Filament Assembly ◽  
Bipolar Filament ◽  
Network Anomalies

This study identifies that disruption of the nuclear lamina via lamin A/C depletion results in contrasting actomyosin cytoskeletal patterning, linked to increased myosin-II filament assembly.

scholarly journals The Aging Vasculature: Glucose Tolerance, Hypoglycemia and the Role of the Serum Response Factor

2021 ◽  
Vol 8 (5) ◽  
pp. 58
Author(s):  
Hazel Aberdeen ◽  
Kaela Battles ◽  
Ariana Taylor ◽  
Jeranae Garner-Donald ◽  
Ana Davis-Wilson ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Molecular Mechanisms ◽  
Serum Response Factor ◽  
Response Factor ◽  
Homeostatic Control ◽  
Older Americans ◽  
The Subject ◽  
Serum Response

The fastest growing demographic in the U.S. at the present time is those aged 65 years and older. Accompanying advancing age are a myriad of physiological changes in which reserve capacity is diminished and homeostatic control attenuates. One facet of homeostatic control lost with advancing age is glucose tolerance. Nowhere is this more accentuated than in the high proportion of older Americans who are diabetic. Coupled with advancing age, diabetes predisposes affected subjects to the onset and progression of cardiovascular disease (CVD). In the treatment of type 2 diabetes, hypoglycemic episodes are a frequent clinical manifestation, which often result in more severe pathological outcomes compared to those observed in cases of insulin resistance, including premature appearance of biomarkers of senescence. Unfortunately, molecular mechanisms of hypoglycemia remain unclear and the subject of much debate. In this review, the molecular basis of the aging vasculature (endothelium) and how glycemic flux drives the appearance of cardiovascular lesions and injury are discussed. Further, we review the potential role of the serum response factor (SRF) in driving glycemic flux-related cellular signaling through its association with various proteins.

scholarly journals Critical Role of Serum Response Factor in Pulmonary Myofibroblast Differentiation Induced by TGF-β

2009 ◽  
Vol 41 (3) ◽  
pp. 332-338 ◽  
Author(s):  
Nathan Sandbo ◽  
Steven Kregel ◽  
Sebastien Taurin ◽  
Sangeeta Bhorade ◽  
Nickolai O. Dulin
Keyword(s):  
Serum Response Factor ◽  
Critical Role ◽  
Myofibroblast Differentiation ◽  
Response Factor ◽  
Serum Response

scholarly journals Enhancement of mDia2 activity by Rho-kinase-dependent phosphorylation of the diaphanous autoregulatory domain

2011 ◽  
Vol 439 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Dean P. Staus ◽  
Joan M. Taylor ◽  
Christopher P. Mack
Keyword(s):  
Smooth Muscle ◽  
Actin Polymerization ◽  
Serum Response Factor ◽  
Rho Kinase ◽  
Specific Gene ◽  
Related Transcription Factor ◽  
Inhibitory Domain ◽  
Serum Response ◽  
Acidic Region ◽  
Basic Region

It is clear that RhoA activates the DRF (diaphanous-related formin) mDia2 by disrupting the molecular interaction between the DAD (diaphanous autoregulatory domain) and the DID (diaphanous inhibitory domain). Previous studies indicate that a basic motif within the DAD contributes to mDia2 auto-inhibition, and results shown in the present study suggest these residues bind a conserved acidic region within the DID. Furthermore, we demonstrate that mDia2 is phosphorylated by ROCK (Rho-kinase) at two conserved residues (Thr1061 and Ser1070) just C-terminal to the DAD basic region. Phosphomimetic mutations to these residues in the context of the full-length molecule enhanced mDia2 activity as measured by increased actin polymerization, SRF (serum response factor)-dependent smooth muscle-specific gene transcription, and nuclear localization of myocardin-related transcription factor B. Biochemical and functional data indicate that the T1061E/S1070E mutation significantly inhibited the ability of DAD to interact with DID and enhanced mDia2 activation by RhoA. Taken together, the results of the present study indicate that ROCK-dependent phosphorylation of the mDia2 DAD is an important determinant of mDia2 activity and that this signalling mechanism affects actin polymerization and smooth muscle cell-specific gene expression.

scholarly journals Myozap, a Novel Intercalated Disc Protein, Activates Serum Response Factor–Dependent Signaling and Is Required to Maintain Cardiac Function In Vivo

2010 ◽  
Vol 106 (5) ◽  
pp. 880-890 ◽  
Author(s):  
Thalia S. Seeger ◽  
Derk Frank ◽  
Claudia Rohr ◽  
Rainer Will ◽  
Steffen Just ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Serum Response Factor ◽  
Response Factor ◽  
Intercalated Disc ◽  
Serum Response
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