scholarly journals Nucleotide dependent differences between the α-skeletal and α-cardiac actin isoforms

2008 ◽  
Vol 368 (3) ◽  
pp. 696-702 ◽  
Author(s):  
József Orbán ◽  
Dénes Lőrinczy ◽  
Miklós Nyitrai ◽  
Gábor Hild
Keyword(s):  
Actin Isoforms ◽  
Cardiac Actin

scholarly journals Cardiac and Skeletal Actin Substrates Uniquely Tune Cardiac Myosin Strain-Dependent Mechanics

2018 ◽  
Author(s):  
Yihua Wang ◽  
Katalin Ajtai ◽  
Thomas P. Burghardt
Keyword(s):  
Resistive Load ◽  
Step Size ◽  
Actin Isoforms ◽  
Cardiac Actin ◽  
N Terminus ◽  
Human Adults ◽  
Force Velocity ◽  
Strain Dependent

ABSTRACTNative cardiac ventricular myosin (βmys) translates actin under load by transducing ATP free energy into mechanical work on actin during muscle contraction. Unitary βmys translation of actin is the myosin step-size. In vitro and in vivo βmys regulates contractile force and velocity by remixing 3 different step-sizes with stepping frequencies autonomously adapted to workload. Cardiac and skeletal actin isoforms have a specific 1:4 stoichiometry in normal adult human ventriculum. Human adults with inheritable hypertrophic cardiomyopathy (HCM) up-regulate skeletal actin in ventriculum suggesting that increasing skeletal/cardiac actin stoichiometry also adapts myosin force-velocity to respond to the muscle’s inability to meet demand.Nanometer scale displacement of quantum dot (Qdot) labeled actin under resistive load when impelled by βmys measures single myosin force-velocity in vitro in the Qdot assay. Unitary displacement classification constraints introduced here better separates myosin based signal from background upgrading step-size spatial resolution to the sub-nanometer range. Single βmys force-velocity for skeletal vs cardiac actin substrates was compared using the Qdot assay.Two competing myosin strain-sensitive mechanisms regulate step-size choices dividing mechanical characteristics into low- and high-force regimes. The actin isoforms alter myosin strain-sensitive regulation such that onset of the high-force regime, where a short step-size is a large or major contributor, is offset to higher loads by a unique cardiac ELC N-terminus/cardiac-actin contact at Glu6/Ser358. It modifies βmys force-velocity by stabilizing the ELC N-terminus/cardiac-actin association. Uneven onset of the high-force regime for skeletal vs cardiac actin dynamically changes force-velocity characteristics as skeletal/cardiac actin fractional content increases in diseased muscle.

scholarly journals Actin Mutations and Their Role in Disease

2020 ◽  
Vol 21 (9) ◽  
pp. 3371 ◽  
Author(s):  
Francine Parker ◽  
Thomas G. Baboolal ◽  
Michelle Peckham
Keyword(s):  
Actin Polymerization ◽  
Eukaryotic Cells ◽  
Actin Isoforms ◽  
Cardiac Actin ◽  
Mutational Hotspots ◽  
Almost All

Actin is a widely expressed protein found in almost all eukaryotic cells. In humans, there are six different genes, which encode specific actin isoforms. Disease-causing mutations have been described for each of these, most of which are missense. Analysis of the position of the resulting mutated residues in the protein reveals mutational hotspots. Many of these occur in regions important for actin polymerization. We briefly discuss the challenges in characterizing the effects of these actin mutations, with a focus on cardiac actin mutations.

scholarly journals Cardiac and skeletal actin substrates uniquely tune cardiac myosin strain-dependent mechanics

Open Biology ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 180143 ◽  
Author(s):  
Yihua Wang ◽  
Katalin Ajtai ◽  
Thomas P. Burghardt
Keyword(s):  
Step Size ◽  
Actin Isoforms ◽  
Essential Light Chain ◽  
Cardiac Actin ◽  
N Terminus ◽  
Human Adults ◽  
Force Velocity ◽  
Strain Dependent

Cardiac ventricular myosin (βmys) translates actin by transducing ATP free energy into mechanical work during muscle contraction. Unitary βmys translation of actin is the step-size. In vitro and in vivo βmys regulates contractile force and velocity autonomously by remixing three different step-sizes with adaptive stepping frequencies. Cardiac and skeletal actin isoforms have a specific 1 : 4 stoichiometry in normal adult human ventriculum. Human adults with inheritable hypertrophic cardiomyopathy (HCM) upregulate skeletal actin in ventriculum probably compensating the diseased muscle's inability to meet demand by adjusting βmys force–velocity characteristics. βmys force–velocity characteristics were compared for skeletal versus cardiac actin substrates using ensemble in vitro motility and single myosin assays. Two competing myosin strain-sensitive mechanisms regulate step-size choices dividing single βmys mechanics into low- and high-force regimes. The actin isoforms alter myosin strain-sensitive regulation such that onset of the high-force regime, where a short step-size is a large or major contributor, is offset to higher loads probably by the unique cardiac essential light chain (ELC) N-terminus/cardiac actin contact at Glu6/Ser358. It modifies βmys force–velocity by stabilizing the ELC N-terminus/cardiac actin association. Uneven onset of the high-force regime for skeletal versus cardiac actin modulates force–velocity characteristics as skeletal/cardiac actin fractional content increases in diseased muscle.

scholarly journals Impaired Expression of Cytoplasmic Actins Leads to Chromosomal Instability of MDA-MB-231 Basal-Like Mammary Gland Cancer Cell Line

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2151
Author(s):  
Vera Dugina ◽  
Galina Shagieva ◽  
Mariya Novikova ◽  
Svetlana Lavrushkina ◽  
Olga Sokova ◽  
...  
Keyword(s):  
Cell Line ◽  
Chromosomal Instability ◽  
Cell Transformation ◽  
Cancer Cell Line ◽  
Neoplastic Cell ◽  
Chromosome Morphology ◽  
Human Carcinoma ◽  
Actin Isoforms ◽  
Cytoplasmic Actin ◽  
Neoplastic Cell Transformation

We have shown previously that two cytoplasmic actin isoforms play different roles in neoplastic cell transformation. Namely, β-cytoplasmic actin acts as a tumor suppressor, whereas γ-cytoplasmic actin enhances malignant features of tumor cells. The distinct participation of each cytoplasmic actin in the cell cycle driving was also observed. The goal of this study was to describe the diverse roles of cytoplasmic actins in the progression of chromosomal instability of MDA-MB-231 basal-like human carcinoma cell line. We performed traditional methods of chromosome visualization, as well as 3D-IF microscopy and western blotting for CENP-A detection/quantification, to investigate chromosome morphology. Downregulation of cytoplasmic actin isoforms alters the phenotype and karyotype of MDA-MB-231 breast cancer cells. Moreover, β-actin depletion leads to the progression of chromosomal instability with endoreduplication and aneuploidy increase. On the contrary, γ-actin downregulation results not only in reduced percentage of mitotic carcinoma cells, but leads to chromosome stability, reduced polyploidy, and aneuploidy.

Phalloidin Binding and Rheological Differences among Actin Isoforms†

Biochemistry ◽  
1996 ◽  
Vol 35 (45) ◽  
pp. 14062-14069 ◽  
Author(s):  
P. G. Allen ◽  
C. B. Shuster ◽  
J. Käs ◽  
C. Chaponnier ◽  
P. A. Janmey ◽  
...  
Keyword(s):  
Actin Isoforms

Abstract 18845: Induced Cardiac Progenitor Cells Differentiate Into Cardiac Lineage Cells in vivo and Improve Survival in Mice post Myocardial Infarction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Pratik A Lalit ◽  
Max R Salick ◽  
Daryl O Nelson ◽  
Jayne M Squirrell ◽  
Christina M Shafer ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Disease Modeling ◽  
Ex Vivo ◽  
Cardiac Progenitor Cells ◽  
Heart Tube ◽  
Whole Embryo Culture ◽  
Cardiac Actin ◽  
Cardiac Lineage

Several studies have reported reprogramming of fibroblasts (Fibs) to induced cardiomyocytes, and we have recently reprogrammed mouse Fibs to induced cardiac progenitor cells (iCPCs), which may be more favorable for cardiac repair because of their expandability and multipotency. Adult cardiac (AC), lung and tail-tip Fibs from an Nkx2.5-EYFP reporter mouse were reprogrammed using a combination of five defined factors into iCPCs. Transcriptome and immunocytochemistry analysis revealed that iCPCs were cardiac mesoderm-restricted progenitors that expressed CPC markers including Nkx2.5, Gata4, Irx4, Tbx5, Cxcr4, Flk1 etc. iCPCs could be extensively expanded (over 30 passages) while maintaining multipotency to differentiate in vitro into cardiac lineage cells including cardiomyocytes (CMs), smooth muscle cells and endothelial cells. iCPC derived CMs upon co-culture with mESC-derived CMs formed intercellular gap junctions, exhibited calcium transients, and contractions. The purpose of this study was to determine the in vivo potency of iCPCs. Given that the Nkx2.5-EYFP reporter identifies embryonic CPCs, we first tested the embryonic potency of iCPCs using an ex vivo whole embryo culture model injecting cells into the cardiac crescent (CC) of E8.5 mouse embryos and culturing for 24 to 48 hours. GFP labeled AC Fibs were first tested and live imaging revealed that after 24 hours these cells were rejected from the embryo proper and localized to the ecto-placental cone. In contrast, iCPCs reprogrammed from AC Fibs when injected into the CC localized to the developing heart tube and differentiated into MLC2v, αMHC and cardiac actin expressing CMs. Further we injected iCPCs into infarcted adult mouse hearts and determined their regenerative potential after 1-4 wks. The iCPCs significantly improved survival (p<0.01 Mantel-Cox test) in treated animals (75%) as compared to control (11%). Immunohistochemistry revealed that injected iCPCs localized to the scar area and differentiated into cardiac lineage cells including CMs (cardiac actin). These results indicate that lineage reprogramming of adult somatic cells into iCPCs provides a scalable cell source for cardiac regenerative therapy as well as drug discovery and disease modeling.

Sign in / Sign up

Export Citation Format

Share Document