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The Cytoskeleton and Its Binding Proteins as Mechanosensors, Transducers, and Functional Regulators of the Cells

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 7807

Special Issue Editor

Prof. Dr. Wan Lee

E-Mail Website
Guest Editor
1. Department of Biochemistry, Dongguk University School of Medicine, Gyeongju 38066, Republic of Korea
2. Channelopathy Research Center (CRC), Dongguk University School of Medicine, Ilsan 10326, Republic of Korea
Interests: mechanotransduction; cytoskeleton remodeling; proliferation; differentiation; myogenesis; sarcopenia; insulin resistance; diabetes; metabolism; glucose metabolism; lipid metabolism; metabolic diseases; energy metabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,  

The cytoskeleton is one of the most dynamic and functionally versatile components, as it is involved in numerous cellular processes, such as force transmission, motility, adhesion, morphogenesis, vesicular transports, cell division, and cell-to-cell communication. Additionally, cytoskeletal proteins, including many cytoskeleton-binding proteins (CBPs), are not only known to be essential regulators of cytoskeleton dynamics, but are also involved in mechanosensing and mechanotransduction, in which mechanical and physical changes are converted into biochemical signals that eventually regulate various cellular responses. From this point of view, they have been suggested as the pivotal player in cell proliferation, migration, differentiation, and survival. Although recent advances in cytoskeletal proteins and their regulators have helped us to understand the crucial roles of cytoskeletal proteins in cell architecture, survival, and functions, it still remains unclear which mechanisms underlie the regulatory function of the cytoskeleton and CBPs.

This Special Issue will explore new insights from the most recent findings, advances, and prospects in all aspects of the cytoskeleton and CBP research. We encourage the submission of original research articles and review articles focused on the structure, types, development, regeneration, and functions regulated by the cytoskeleton and CBPs. We especially welcome discoveries related to mechanosensing, mechanotransduction, and responding behaviors mediated by the cytoskeleton and CBPs. Understanding the interplay between biochemical and mechanical changes of the cytoskeletal components will give us important insight into the molecular mechanisms of diverse functions, including cell migration, proliferation, and differentiation, in both physiological and pathological processes.

Prof. Dr. Wan Lee
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cytoskeleton
  • cytoskeleton-binding protein
  • cytoskeletal protein
  • cell signaling
  • mechanotransduction
  • proliferation
  • migration
  • motility
  • differentiation
  • structure

Published Papers (6 papers)

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Editorial

Jump to: Research, Review, Other

3 pages, 167 KiB  
Editorial
The Cytoskeleton and Its Binding Proteins as Mechanosensors, Transducers, and Functional Regulators of Cells
by Wan Lee
Int. J. Mol. Sci. 2024, 25(1), 172; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25010172 - 22 Dec 2023
Viewed by 575
Abstract
Due to its complement of diverse proteins, such as actin filaments, intermediate filaments, and microtubules, the cytoskeleton is essential not only for structural stability but also for regulating cellular signaling, intracellular transportation, and cell division [...] Full article
(This article belongs to the Special Issue The Cytoskeleton and Its Binding Proteins as Mechanosensors, Transducers, and Functional Regulators of the Cells)

Research

Jump to: Editorial, Review, Other

13 pages, 2624 KiB  
Article
FLII Modulates the Myogenic Differentiation of Progenitor Cells via Actin Remodeling-Mediated YAP1 Regulation
by Mai Thi Nguyen, Quoc Kiet Ly, Hyun-Jung Kim and Wan Lee
Int. J. Mol. Sci. 2023, 24(18), 14335; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241814335 - 20 Sep 2023
Cited by 1 | Viewed by 870
Abstract
The dynamic rearrangement of the actin cytoskeleton plays an essential role in myogenesis, which is regulated by diverse mechanisms, such as mechanotransduction, modulation of the Hippo signaling pathway, control of cell proliferation, and the influence of morphological changes. Despite the recognized importance of [...] Read more.
The dynamic rearrangement of the actin cytoskeleton plays an essential role in myogenesis, which is regulated by diverse mechanisms, such as mechanotransduction, modulation of the Hippo signaling pathway, control of cell proliferation, and the influence of morphological changes. Despite the recognized importance of actin-binding protein Flightless-1 (FLII) during actin remodeling, the role played by FLII in the differentiation of myogenic progenitor cells has not been explored. Here, we investigated the roles of FLII in the proliferation and differentiation of myoblasts. FLII was found to be enriched in C2C12 myoblasts, and its expression was stable during the early stages of differentiation but down-regulated in fully differentiated myotubes. Knockdown of FLII in C2C12 myoblasts resulted in filamentous actin (F-actin) accumulation and inhibited Yes-associated protein 1 (YAP1) phosphorylation, which triggers its nuclear translocation from the cytoplasm. Consequently, the expressions of YAP1 target genes, including PCNA, CCNB1, and CCND1, were induced, and the cell cycle and proliferation of myoblasts were promoted. Moreover, FLII knockdown significantly inhibited the expression of myogenic regulatory factors, i.e., MyoD and MyoG, thereby impairing myoblast differentiation, fusion, and myotube formation. Thus, our findings demonstrate that FLII is crucial for the differentiation of myoblasts via modulation of the F-actin/YAP1 axis and suggest that FLII is a putative novel therapeutic target for muscle wasting. Full article
(This article belongs to the Special Issue The Cytoskeleton and Its Binding Proteins as Mechanosensors, Transducers, and Functional Regulators of the Cells)
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Review

Jump to: Editorial, Research, Other

33 pages, 2429 KiB  
Review
Effects of Mechanical Stress on Endothelial Cells In Situ and In Vitro
by Kazuo Katoh
Int. J. Mol. Sci. 2023, 24(22), 16518; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242216518 - 20 Nov 2023
Cited by 1 | Viewed by 1126
Abstract
Endothelial cells lining blood vessels are essential for maintaining vascular homeostasis and mediate several pathological and physiological processes. Mechanical stresses generated by blood flow and other biomechanical factors significantly affect endothelial cell activity. Here, we review how mechanical stresses, both in situ and [...] Read more.
Endothelial cells lining blood vessels are essential for maintaining vascular homeostasis and mediate several pathological and physiological processes. Mechanical stresses generated by blood flow and other biomechanical factors significantly affect endothelial cell activity. Here, we review how mechanical stresses, both in situ and in vitro, affect endothelial cells. We review the basic principles underlying the cellular response to mechanical stresses. We also consider the implications of these findings for understanding the mechanisms of mechanotransducer and mechano-signal transduction systems by cytoskeletal components. Full article
(This article belongs to the Special Issue The Cytoskeleton and Its Binding Proteins as Mechanosensors, Transducers, and Functional Regulators of the Cells)
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21 pages, 1305 KiB  
Review
Nucleus Mechanosensing in Cardiomyocytes
by Isabella Leite Coscarella, Maicon Landim-Vieira, Hosna Rastegarpouyani, Prescott Bryant Chase, Jerome Irianto and Jose Renato Pinto
Int. J. Mol. Sci. 2023, 24(17), 13341; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241713341 - 28 Aug 2023
Cited by 2 | Viewed by 1648
Abstract
Cardiac muscle contraction is distinct from the contraction of other muscle types. The heart continuously undergoes contraction–relaxation cycles throughout an animal’s lifespan. It must respond to constantly varying physical and energetic burdens over the short term on a beat-to-beat basis and relies on [...] Read more.
Cardiac muscle contraction is distinct from the contraction of other muscle types. The heart continuously undergoes contraction–relaxation cycles throughout an animal’s lifespan. It must respond to constantly varying physical and energetic burdens over the short term on a beat-to-beat basis and relies on different mechanisms over the long term. Muscle contractility is based on actin and myosin interactions that are regulated by cytoplasmic calcium ions. Genetic variants of sarcomeric proteins can lead to the pathophysiological development of cardiac dysfunction. The sarcomere is physically connected to other cytoskeletal components. Actin filaments, microtubules and desmin proteins are responsible for these interactions. Therefore, mechanical as well as biochemical signals from sarcomeric contractions are transmitted to and sensed by other parts of the cardiomyocyte, particularly the nucleus which can respond to these stimuli. Proteins anchored to the nuclear envelope display a broad response which remodels the structure of the nucleus. In this review, we examine the central aspects of mechanotransduction in the cardiomyocyte where the transmission of mechanical signals to the nucleus can result in changes in gene expression and nucleus morphology. The correlation of nucleus sensing and dysfunction of sarcomeric proteins may assist the understanding of a wide range of functional responses in the progress of cardiomyopathic diseases. Full article
(This article belongs to the Special Issue The Cytoskeleton and Its Binding Proteins as Mechanosensors, Transducers, and Functional Regulators of the Cells)
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17 pages, 1066 KiB  
Review
Fascin-1 in Cancer Cell Metastasis: Old Target-New Insights
by Eleonora Sarantelli, Apostolis Mourkakis, Lefteris C. Zacharia, Andreas Stylianou and Vasiliki Gkretsi
Int. J. Mol. Sci. 2023, 24(14), 11253; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241411253 - 08 Jul 2023
Cited by 3 | Viewed by 1946
Abstract
As metastasis is responsible for most cancer-related deaths, understanding the cellular and molecular events that lead to cancer cell migration and invasion will certainly provide insights into novel anti-metastatic therapeutic targets. Fascin-1 is an actin-bundling protein fundamental to all physiological or pathological processes [...] Read more.
As metastasis is responsible for most cancer-related deaths, understanding the cellular and molecular events that lead to cancer cell migration and invasion will certainly provide insights into novel anti-metastatic therapeutic targets. Fascin-1 is an actin-bundling protein fundamental to all physiological or pathological processes that require cell migration. It is responsible for cross-linking actin microfilaments during the formation of actin-rich cellular structures at the leading edge of migrating cells such as filopodia, lamellipodia and invadopodia. While most epithelial tissues express low levels of Fascin-1, it is dramatically elevated in the majority of cancers and its expression has been associated with more aggressive disease and decreased overall survival. Hence, it has been proposed as a potential anti-cancer target. In the present review, we studied recent literature with regard to Fascin-1 expression in different cancers, its role in altering the mechanical properties of cancer cells, promoting cancer cell migration, invasion and metastasis and the effect of its inhibition, via various pharmacological inhibitors, in eliminating metastasis in vitro and/or in vivo. Recent studies corroborate the notion that Fascin-1 is critically involved in metastasis and prove that it is a valuable anti-metastatic target that is worth investigating further. Full article
(This article belongs to the Special Issue The Cytoskeleton and Its Binding Proteins as Mechanosensors, Transducers, and Functional Regulators of the Cells)
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Other

12 pages, 1077 KiB  
Perspective
The Potential for Targeting AVIL and Other Actin-Binding Proteins in Rhabdomyosarcoma
by Robert Cornelison, Laine Marrah, Adelaide Fierti, Claire Piczak, Martyna Glowczyk, Anam Tajammal, Sarah Lynch and Hui Li
Int. J. Mol. Sci. 2023, 24(18), 14196; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241814196 - 17 Sep 2023
Viewed by 1124
Abstract
Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue cancer with a survival rate below 27% for high-risk children despite aggressive multi-modal therapeutic interventions. After decades of research, no targeted therapies are currently available. Therapeutically targeting actin-binding proteins, although promising, has historically been challenging. [...] Read more.
Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue cancer with a survival rate below 27% for high-risk children despite aggressive multi-modal therapeutic interventions. After decades of research, no targeted therapies are currently available. Therapeutically targeting actin-binding proteins, although promising, has historically been challenging. Recent advances have made this possibility more salient, including our lab’s identification of advillin (AVIL), a novel oncogenic actin-binding protein that plays a role in many cytoskeletal functions. AVIL is overexpressed in many RMS cell lines, patient-derived xenograft models, and a cohort of 30 clinical samples of both the alveolar (ARMS) and embryonal (ERMS) subtypes. Overexpression of AVIL in mesenchymal stem cells induces neoplastic transformation both in vitro and in vivo, and reversing overexpression through genetic modulation reverses the transformation. This suggests a critical role of AVIL in RMS tumorigenesis and maintenance. As an actin-binding protein, AVIL would not traditionally be considered a druggable target. This perspective will address the feasibility of targeting differentially expressed actin-binding proteins such as AVIL therapeutically, and how critical cell infrastructure can be damaged in a cancer-specific manner. Full article
(This article belongs to the Special Issue The Cytoskeleton and Its Binding Proteins as Mechanosensors, Transducers, and Functional Regulators of the Cells)
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