Diversity of microtubule arrays in animal cells at a glance

Journal of Cell Science, Journal Year: 2025, Volume and Issue: 138(3)

Published: Feb. 1, 2025

ABSTRACT Microtubules are cytoskeletal filaments important for various cellular processes such as intracellular transport, cell division, polarization and migration. Microtubule organization goes hand in with function. Motile cells, immune cells or fibroblasts, contain microtubule asters attached to the centrosome Golgi complex, whereas many other differentiated microtubules form linear arrays meshworks anchored at membrane-bound organelles cortex. Over past decade, new developments culture, genome editing microscopy have greatly advanced our understanding of complex arrays. In this Cell Science a Glance article accompanying poster, we review diversity interphase animal cells. We describe network geometries present explore variety microtubule-organizing centers responsible these geometries, discuss examples reorganization response functional changes their interplay motility tissue development.

Language: Английский

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Phosphoproteomics Profiling Defines a Target Landscape of the Basophilic Protein Kinases AKT, S6K, and RSK in Skeletal Myotubes

Journal of Proteome Research, Journal Year: 2023, Volume and Issue: 22(3), P. 768 - 789

Published: Feb. 10, 2023

Phosphorylation-dependent signal transduction plays an important role in regulating the functions and fate of skeletal muscle cells. Central players phospho-signaling network are protein kinases AKT, S6K, RSK as part PI3K-AKT-mTOR-S6K RAF-MEK-ERK-RSK pathways. However, despite their functional importance, knowledge about specific targets is incomplete because these share same basophilic substrate motif RxRxxp[ST]. To address this, we performed a multifaceted quantitative phosphoproteomics study myotubes following kinase inhibition. Our data corroborate cross talk between AKT RAF, negative feedback loop on ERK, putative connection PI3K signaling. Altogether, report target landscape containing 49 so far unknown sites. phosphorylate numerous proteins involved development, integrity, functions, signaling converges factors that central for cytoskeleton. Whereas controls insulin impinges GTPase signaling, nuclear characteristic RSK. further support glucose metabolism. Shared have RNA maturation, stability, translation, which suggests establish intricate to orchestrate regulate processes translation.

Language: Английский

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LINCing Nuclear Mechanobiology With Skeletal Muscle Mass and Function

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: July 21, 2021

Skeletal muscle demonstrates a high degree of adaptability in response to changes mechanical input. The phenotypic transformation cues includes mass and force generating capabilities, yet the molecular pathways that govern skeletal adaptation are still incompletely understood. While there is strong evidence mechanotransduction stimulate protein synthesis play key role regulation mass, likely additional mechano-sensitive mechanisms important for controlling functional adaptation. There emerging cell nucleus can directly respond signals (i.e., nuclear mechanotransduction), providing potential level cellular mass. importance function evident by various genetic diseases arise from mutations proteins crucial transmission between cytoskeleton nucleus. Intriguingly, these preferentially affect cardiac muscle, suggesting critically striated homeostasis. Here we discuss our current understanding how acts as mechanosensor, describe main cytoskeletal involved process, propose similar mechanoresponsive could occur unique environment myofiber. In addition, examine fits into framework stimuli regulates

Language: Английский

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

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

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Loss of connectin novex-3 leads to heart dysfunction associated with impaired cardiomyocyte proliferation and abnormal nuclear mechanics

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 14, 2024

Connectin (also known as titin) is a giant striated muscle protein that functions molecular spring by providing elasticity to the sarcomere. Novex-3 short splice variant of connectin whose physiological function remains unknown. We have recently demonstrated using in vitro analyses addition sarcomere expression, novex-3 was also expressed cardiomyocyte nuclei exclusively during fetal life, where it provides elasticity/compliance and promotes proliferation fetus, suggesting non-sarcomeric function. Here, we analyzed knockout mice assess involvement this cardiac pathophysiology vivo. Deficiency compromised induced enlargement individual cardiomyocytes neonates. In adults, deficiency resulted chamber dilation systolic dysfunction, associated with Ca2+ dysregulation, resulting reduced life span. Mechanistic revealed possible association between impaired abnormal nuclear mechanics, including stiffer positioned peripherally stabilized circumnuclear microtubules cardiomyocytes. Although underlying causal relationships were not fully elucidated, these data show has vital serves an early contributor proliferation.

Language: Английский

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