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Essays in Biochemistry Oct 2019Directed cell migration is critical for embryogenesis and organ development, wound healing and the immune response. Microtubules are dynamic polymers that control... (Review)
Review
Directed cell migration is critical for embryogenesis and organ development, wound healing and the immune response. Microtubules are dynamic polymers that control directional migration through a number of coordinated processes: microtubules are the tracks for long-distance intracellular transport, crucial for delivery of new membrane components and signalling molecules to the leading edge of a migrating cell and the recycling of adhesion receptors. Microtubules act as force generators and compressive elements to support sustained cell protrusions. The assembly and disassembly of microtubules is coupled to Rho GTPase signalling, thereby controlling actin polymerisation, myosin-driven contractility and the turnover of cellular adhesions locally. Cross-talk of actin and microtubule dynamics is mediated through a number of common binding proteins and regulators. Furthermore, cortical microtubule capture sites are physically linked to focal adhesions, facilitating the delivery of secretory vesicles and efficient cross-talk. Here we summarise the diverse functions of microtubules during cell migration, aiming to show how they contribute to the spatially and temporally coordinated sequence of events that permit efficient, directional and persistent migration.
Topics: Actin Cytoskeleton; Actins; Cell Adhesion; Cell Movement; Focal Adhesions; Humans; Microtubules; Signal Transduction; rho GTP-Binding Proteins
PubMed: 31358621
DOI: 10.1042/EBC20190016 -
Journal of Cellular Physiology May 2022Mitochondria perform diverse functions in the cell and their roles during processes such as cell survival, differentiation, and migration are increasingly being... (Review)
Review
Mitochondria perform diverse functions in the cell and their roles during processes such as cell survival, differentiation, and migration are increasingly being appreciated. Mitochondrial and actin cytoskeletal networks not only interact with each other, but this multifaceted interaction shapes their functional dynamics. The interrelation between mitochondria and the actin cytoskeleton extends far beyond the requirement of mitochondrial ATP generation to power actin dynamics, and impinges upon several major aspects of cellular physiology. Being situated at the hub of cell signaling pathways, mitochondrial function can alter the activity of actin regulatory proteins and therefore modulate the processes downstream of actin dynamics such as cellular migration. As we will discuss, this regulation is highly nuanced and operates at multiple levels allowing mitochondria to occupy a strategic position in the regulation of migration, as well as pathological events that rely on aberrant cell motility such as cancer metastasis. In this review, we summarize the crosstalk that exists between mitochondria and actin regulatory proteins, and further emphasize on how this interaction holds importance in cell migration in normal as well as dysregulated scenarios as in cancer.
Topics: Actin Cytoskeleton; Actins; Cell Movement; Humans; Mitochondria; Neoplasms
PubMed: 35342955
DOI: 10.1002/jcp.30729 -
The EMBO Journal Apr 2021The identification of Tunneling Nanotubes (TNTs) and TNT-like structures signified a critical turning point in the field of cell-cell communication. With hypothesized... (Review)
Review
The identification of Tunneling Nanotubes (TNTs) and TNT-like structures signified a critical turning point in the field of cell-cell communication. With hypothesized roles in development and disease progression, TNTs' ability to transport biological cargo between distant cells has elevated these structures to a unique and privileged position among other mechanisms of intercellular communication. However, the field faces numerous challenges-some of the most pressing issues being the demonstration of TNTs in vivo and understanding how they form and function. Another stumbling block is represented by the vast disparity in structures classified as TNTs. In order to address this ambiguity, we propose a clear nomenclature and provide a comprehensive overview of the existing knowledge concerning TNTs. We also discuss their structure, formation-related pathways, biological function, as well as their proposed role in disease. Furthermore, we pinpoint gaps and dichotomies found across the field and highlight unexplored research avenues. Lastly, we review the methods employed to date and suggest the application of new technologies to better understand these elusive biological structures.
Topics: Actin Cytoskeleton; Animals; Cell Communication; Cell Surface Extensions; Humans; Nanotubes
PubMed: 33646572
DOI: 10.15252/embj.2020105789 -
Current Opinion in Cell Biology Feb 2021Cortical actin waves have emerged as a widely prevalent phenomena and brought pattern formation to many fields of cell biology. Cortical excitabilities, reminiscent of... (Review)
Review
Cortical actin waves have emerged as a widely prevalent phenomena and brought pattern formation to many fields of cell biology. Cortical excitabilities, reminiscent of the electric excitability in neurons, are likely fundamental property of the cell cortex. Although they have been mostly considered to be biochemical in nature, accumulating evidence support the role of mechanics in the pattern formation process. Both pattern formation and mechanobiology approach biological phenomena at the collective level, either by looking at the mesoscale dynamical behavior of molecular networks or by using collective physical properties to characterize biological systems. As such they are very different from the traditional reductionist, bottom-up view of biology, which brings new challenges and potential opportunities. In this essay, we aim to provide our perspectives on what the proposed mechanochemical feedbacks are and open questions regarding their role in cortical excitable and oscillatory dynamics.
Topics: Actin Cytoskeleton; Animals; Biomechanical Phenomena; Cell Membrane; Cell Physiological Phenomena; Cytoplasm; Eukaryotic Cells; Feedback, Physiological
PubMed: 33039945
DOI: 10.1016/j.ceb.2020.08.017 -
Cold Spring Harbor Perspectives in... Aug 2022Wound healing requires a complex cascade of highly controlled and conserved cellular and molecular processes. These involve numerous cell types and extracellular matrix... (Review)
Review
Wound healing requires a complex cascade of highly controlled and conserved cellular and molecular processes. These involve numerous cell types and extracellular matrix molecules regulated by the actin cytoskeleton. This microscopic network of filaments is present within the cytoplasm of all cells and provides the shape and mechanical support required for cell movement and proliferation. Here, an overview of the processes of wound healing are described from the perspective of the cell in relation to the actin cytoskeleton. Key points of discussion include the role of actin, its binding proteins, signaling pathways, and events that play significant roles in the phases of wound healing. The identification of cytoskeletal targets that can be used to manipulate and improve wound healing is included as an emerging area of focus that may inform future therapeutic approaches to improve healing of complex wounds.
Topics: Actin Cytoskeleton; Actins; Cell Movement; Cytoskeleton; Wound Healing
PubMed: 35074864
DOI: 10.1101/cshperspect.a041235 -
The FEBS Journal Mar 2021Fascin is an F-actin-bundling protein that cross-links individual actin filaments into straight and stiff bundles. Fascin overexpression in cancer is strongly associated... (Review)
Review
Fascin is an F-actin-bundling protein that cross-links individual actin filaments into straight and stiff bundles. Fascin overexpression in cancer is strongly associated with poor prognosis and metastatic progression across different cancer types. It is well established that fascin plays a causative role in promoting metastatic progression. We will review the recent progress in our understanding of mechanisms underlying fascin-mediated cancer metastasis. This review will cover the biochemical basis for fascin-bundling activity, the mechanisms by which cancer cells upregulate fascin expression and the mechanism underlying fascin-mediated cancer cell migration, invasion, and metastatic colonization. We propose that fascin has broad roles in both metastatic dissemination and metastatic colonization. Understanding these mechanisms will be crucial to the development of anti-metastasis therapeutics targeting fascin.
Topics: Actin Cytoskeleton; Actins; Animals; Carrier Proteins; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Microfilament Proteins; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms; Neoplastic Cells, Circulating; Protein Isoforms; Signal Transduction; Transcription, Genetic; Tumor Microenvironment
PubMed: 32657526
DOI: 10.1111/febs.15484 -
Cells Mar 2023Since the discovery of their role in the regulation of actin cytoskeleton 30 years ago, Rho GTPases have taken center stage in cell motility research [...].
Since the discovery of their role in the regulation of actin cytoskeleton 30 years ago, Rho GTPases have taken center stage in cell motility research [...].
Topics: rho GTP-Binding Proteins; Actin Cytoskeleton; Cell Movement
PubMed: 36899915
DOI: 10.3390/cells12050779 -
Pediatric Nephrology (Berlin, Germany) Sep 2021The selectivity of the glomerular filter is established by physical, chemical, and signaling interplay among its three core constituents: glomerular endothelial cells,... (Review)
Review
The selectivity of the glomerular filter is established by physical, chemical, and signaling interplay among its three core constituents: glomerular endothelial cells, the glomerular basement membrane, and podocytes. Functional impairment or injury of any of these three components can lead to proteinuria. Podocytes are injured in many forms of human and experimental glomerular disease, including minimal change disease, focal segmental glomerulosclerosis, and diabetes mellitus. One of the earliest signs of podocyte injury is loss of their distinct structure, which is driven by dysregulated dynamics of the actin cytoskeleton. The status of the actin cytoskeleton in podocytes depends on a set of actin binding proteins, nucleators and inhibitors of actin polymerization, and regulatory GTPases. Mutations that alter protein function in each category have been implicated in glomerular diseases in humans and animal models. In addition, a growing body of studies suggest that pharmacological modifications of the actin cytoskeleton have the potential to become novel therapeutics for podocyte-dependent chronic kidney diseases. This review presents an overview of the essential proteins that establish actin cytoskeleton in podocytes and studies demonstrating the feasibility of drugging actin cytoskeleton in kidney diseases.
Topics: Actin Cytoskeleton; Animals; Humans; Podocytes
PubMed: 33188449
DOI: 10.1007/s00467-020-04812-z -
Molecular and Biochemical Parasitology May 2020Trypanosomatids are a monophyletic group of parasitic flagellated protists belonging to the order Kinetoplastida. Their cytoskeleton is primarily made up of microtubules... (Review)
Review
Trypanosomatids are a monophyletic group of parasitic flagellated protists belonging to the order Kinetoplastida. Their cytoskeleton is primarily made up of microtubules in which no actin microfilaments have been detected. Although all these parasites contain actin, it is widely thought that their actin cytoskeleton is reduced when compared to most eukaryotic organisms. However, there is increasing evidence that it is more complex than previously thought. As in other eukaryotic organisms, trypanosomatids encode for a conventional actin that is expected to form microfilament-like structures, and for members of three conserved actin-related proteins probably involved in microfilament nucleation (ARP2, ARP3) and in gene expression regulation (ARP6). In addition to these canonical proteins, also encode for an expanded set of actins and actin-like proteins that seem to be restricted to kinetoplastids. Analysis of their amino acid sequences demonstrated that, although very diverse in primary sequence when compared to actins of model organisms, modelling of their tertiary structure predicted the presence of the actin fold in all of them. Experimental characterization has been done for only a few of the trypanosomatid actins and actin-binding proteins. The most studied is the conventional actin of Leishmania donovani (LdAct), which unusually requires both ATP and Mg for polymerization, unlike other conventional actins that do not require ATP. Additionally, polymerized LdAct tends to assemble in bundles rather than in single filaments. Regulation of actin polymerization depends on their interaction with actin-binding proteins. In trypanosomatids, there is a reduced but sufficient core of actin-binding proteins to promote microfilament nucleation, turnover and stabilization. There are also genes encoding for members of two families of myosin motor proteins, including one lineage-specific. Homologues to all identified actin-family proteins and actin-binding proteins of trypanosomatids are also present in Paratrypanosoma confusum (an early branching trypanosomatid) and in Bodo saltans (a closely related free-living organism belonging to the trypanosomatid sister order of Bodonida) suggesting they were all present in their common ancestor. Secondary losses of these genes may have occurred during speciation within the trypanosomatids, with salivarian trypanosomes having lost many of them and stercorarian trypanosomes retaining most.
Topics: Actin Cytoskeleton; Actins; Animals; Binding Sites; Gene Expression; Humans; Microfilament Proteins; Models, Molecular; Myosins; Phylogeny; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Protozoan Proteins; Trypanosomatina
PubMed: 32353561
DOI: 10.1016/j.molbiopara.2020.111278 -
ELife Jul 2022Experiments using purified proteins reveal how the network of filaments that underlie cell movement becomes denser when pushing against a stronger mechanical force.
Experiments using purified proteins reveal how the network of filaments that underlie cell movement becomes denser when pushing against a stronger mechanical force.
Topics: Actin Cytoskeleton; Actin-Related Protein 2-3 Complex; Actins; Cell Movement; Cytoskeleton
PubMed: 35894589
DOI: 10.7554/eLife.81108