Switching in the expression pattern of actin isoforms marks the onset of contractility and distinct mechanodynamic behavior during cardiomyocyte differentiation DOI Creative Commons

Ricardo H. Pires,

Tung Huy Dau,

Emmanuel Manu

et al.

Physiological Reports, Journal Year: 2022, Volume and Issue: 10(3)

Published: Feb. 1, 2022

Differentiation of cardiac progenitor cells (CPC) into cardiomyocytes is a fundamental step in cardiogenesis, which marked by changes gene expression responsible for remodeling the cytoskeleton and altering mechanical properties cells. Here we have induced differentiation CPC derived from human pluripotent stem immature (iCM) compare with more differentiated (mCM). Using atomic force microscopy real-time deformability cytometry, describe mechanodynamic that occur during process link our findings to protein data cytoskeletal proteins. Increased levels cardiac-specific markers as well evolution morphology contractility parameters correlated expected extent cell was accompanied hypertrophic growth These were associated switching balance different actin isoforms where β-actin predominantly found CPC, smooth muscle α-actin dominant iCM sarcomeric significantly higher mCM. We these differences mechano-dynamic behavior translate Young's modulus depend on adherence. Our results demonstrate intracellular isoform can be used sensitive ruler determine stage early phases cardiomyocyte correlates an increased proteins cellular elasticity.

Language: Английский

Microvascular and macrovascular complications of type 2 diabetes mellitus: Exome wide association analyses DOI Creative Commons
Afnan Mansour, Mira Mousa, Dima Abdelmannan

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: March 23, 2023

Type 2 diabetes mellitus (T2DM) is a chronic, metabolic disorder in which concomitant insulin resistance and β-cell impairment lead to hyperglycemia, influenced by genetic environmental factors. T2DM associated with long-term complications that have contributed the burden of morbidity mortality worldwide. The objective this manuscript conduct an Exome-Wide Association Study (EWAS) on Emirati individuals improve our understanding diabetes-related early diagnostic methods treatment strategies.

Language: Английский

Citations

58
The microtubule cytoskeleton in cardiac mechanics and heart failure DOI
Matthew A. Caporizzo, Benjamin L. Prosser

Nature Reviews Cardiology, Journal Year: 2022, Volume and Issue: 19(6), P. 364 - 378

Published: April 19, 2022

Language: Английский

Citations

64
Dysregulation of extracellular vesicle protein cargo in female myalgic encephalomyelitis/chronic fatigue syndrome cases and sedentary controls in response to maximal exercise DOI Creative Commons
Ludovic Giloteaux, Katherine A. Glass, Arnaud Germain

et al.

Journal of Extracellular Vesicles, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 1, 2024

In healthy individuals, physical exercise improves cardiovascular health and muscle strength, alleviates fatigue reduces the risk of chronic diseases. Although is suggested as a lifestyle intervention to manage various illnesses, it negatively affects people with myalgic encephalomyelitis/chronic syndrome (ME/CFS), who suffer from intolerance. We hypothesized that altered extracellular vesicle (EV) signalling in ME/CFS patients after an challenge may contribute their prolonged exacerbated negative response exertion (post-exertional malaise). EVs were isolated by size exclusion chromatography plasma 18 female 17 age- BMI-matched sedentary controls at three time points: before, 15 min, 24 h maximal cardiopulmonary test. characterized using nanoparticle tracking analysis protein cargo was quantified Tandem Mass Tag-based (TMT) proteomics. The results show EV proteome differently than individuals changes proteins are strongly correlated symptom severity ME/CFS. Differentially abundant versus involved many pathways systems, including coagulation processes, contraction (both smooth skeletal muscle), cytoskeletal proteins, immune system brain signalling.

Language: Английский

Citations

7
AKAP6 orchestrates the nuclear envelope microtubule-organizing center by linking golgi and nucleus via AKAP9 DOI Creative Commons
Silvia Vergarajauregui, Robert Becker, Ulrike Steffen

et al.

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Dec. 9, 2020

The switch from centrosomal microtubule-organizing centers (MTOCs) to non-centrosomal MTOCs during differentiation is poorly understood. Here, we identify AKAP6 as key component of the nuclear envelope MTOC. In rat cardiomyocytes, anchors proteins through its spectrin repeats, acting an adaptor between nesprin-1α and Pcnt or AKAP9. addition, AKAP9 form a protein platform tethering Golgi nucleus. Both exhibit MTOC activity utilizing either AKAP9, Pcnt-AKAP9, respectively. also required for formation in human osteoclasts. Moreover, ectopic expression epithelial cells sufficient recruit endogenous proteins. Finally, cardiomyocyte hypertrophy osteoclast bone resorption activity. Collectively, decipher at bi-layered structure generating two pools microtubules with organizer.

Language: Английский

Citations

43
Archaeal Origins of Eukaryotic Cell and Nucleus DOI
František Baluška,

Sherrie Lyons

Biosystems, Journal Year: 2021, Volume and Issue: 203, P. 104375 - 104375

Published: Feb. 5, 2021

Language: Английский

Citations

40
Functional Coordination among the Golgi Complex, the Centrosome and the Microtubule Cytoskeleton during the Cell Cycle DOI Creative Commons
Fabiola Mascanzoni,

Roberta Iannitti,

Antonino Colanzi

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(3), P. 354 - 354

Published: Jan. 21, 2022

The Golgi complex of mammalian cells is organized in a ribbon-like structure often closely associated with the centrosome during interphase. Conversely, assumes fragmented and dispersed configuration away from mitosis. relative position to are dynamically regulated by microtubules. Many pieces evidence reveal that this microtubule-mediated dynamic association between functional significance cell polarization division. Here, we summarize findings indicating how cooperate organizing microtubule network for directional protein transport positioning required regulating fundamental division processes.

Language: Английский

Citations

24
Nesprin proteins: bridging nuclear envelope dynamics to muscular dysfunction DOI Creative Commons

Zhou Zi-yi,

Qin Qin,

Zhou Fei

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 2, 2024

Abstract This review presents a comprehensive exploration of the pivotal role played by Linker Nucleoskeleton and Cytoskeleton (LINC) complex, with particular focus on Nesprin proteins, in cellular mechanics pathogenesis muscular diseases. Distinguishing itself from prior works, analysis delves deeply into intricate interplay LINC emphasizing its indispensable contribution to maintaining structural integrity, especially mechanically sensitive tissues such as cardiac striated muscles. Additionally, significant association between mutations proteins onset Dilated Cardiomyopathy (DCM) Emery-Dreifuss Muscular Dystrophy (EDMD) is highlighted, underscoring their disease pathogenesis. Through examination DCM EDMD cases, elucidates disruptions nuclear morphology alterations, developmental disorders, thus essential function an intact complex preserving muscle physiological functions. Moreover, provides novel insights implications for dynamics diseases, particularly functional integrity. Furthermore, advanced therapeutic strategies, including rectifying gene mutations, controlling protein expression, enhancing functionality, augmenting cell are proposed. By shedding light molecular mechanisms underlying nuclear-cytoskeletal interactions, lays groundwork future research interventions aimed at addressing genetic disorders.

Language: Английский

Citations

6
Self-Organization of Cellular Units DOI
Timothy J. Mitchison, Christine M. Field

Annual Review of Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 37(1), P. 23 - 41

Published: June 29, 2021

The purpose of this review is to explore self-organizing mechanisms that pattern microtubules (MTs) and spatially organize animal cell cytoplasm, inspired by recent experiments in frog egg extract. We start reviewing conceptual distinctions between templating for subcellular organization. then discuss generate radial MT arrays centers the absence centrosomes. These include autocatalytic nucleation, transport minus ends, nucleation from organelles such as melanosomes Golgi vesicles are also dynein cargoes. partition cytoplasm syncytia, which multiple nuclei share a common starting with cytokinesis, when all metazoan cells transiently syncytial. eggs partitioned prior cytokinesis two modules, protein regulator 1 (PRC1)-kinesin family member 4A (KIF4A) chromosome passenger complex (CPC)-KIF20A. Similar modules may longer-lasting early Drosophila embryos. end discussing shared principles MT-based self-organization cellular units.

Language: Английский

Citations

32
Nesprin-1: novel regulator of striated muscle nuclear positioning and mechanotransduction DOI Creative Commons

Shanelle De Silva,

Zhijuan Fan,

Baoqiang Kang

et al.

Biochemical Society Transactions, Journal Year: 2023, Volume and Issue: 51(3), P. 1331 - 1345

Published: May 12, 2023

Nesprins (nuclear envelope spectrin repeat proteins) are multi-isomeric scaffolding proteins. Giant nesprin-1 and -2 localise to the outer nuclear membrane, interact with SUN (Sad1p/UNC-84) domain-containing proteins at inner membrane form LInker of Nucleoskeleton Cytoskeleton (LINC) complex, which, in association lamin A/C emerin, mechanically couples nucleus cytoskeleton. Despite ubiquitous expression nesprin giant isoforms, pathogenic mutations associated tissue-specific disorders, particularly related striated muscle such as dilated cardiomyopathy Emery-Dreifuss muscular dystrophy. Recent evidence suggests this muscle-specificity might be attributable part, small specific isoform, nesprin-1α2, which has a novel role function. Our current understanding muscle-specific functions its isoforms will summarised review provide insight into potential pathological mechanisms nesprin-related disease may inform targets therapeutic modulation.

Language: Английский

Citations

13
Effects of mutant lamins on nucleo-cytoskeletal coupling in Drosophila models of LMNA muscular dystrophy DOI Creative Commons

Nicholas M. Shaw,

Jose L. Rios-Monterrosa,

Gregory R. Fedorchak

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Aug. 31, 2022

The nuclei of multinucleated skeletal muscles experience substantial external force during development and muscle contraction. Protection from such forces is partly provided by lamins, intermediate filaments that form a scaffold lining the inner nuclear membrane. Lamins play myriad roles, including maintenance shape stability, mediation mechanoresponses, nucleo-cytoskeletal coupling. Herein, we investigate how disease-causing mutant lamins alter myonuclear properties in response to mechanical force. This was accomplished

Language: Английский

Citations

17