Cells

Editorial

Jump to: Research, Review, Other

2 pages, 192 KiB

Open AccessEditorial

Actin-Myosin Cytoskeleton Regulation and Function

by Michael F. Olson

Cells 2023, 12(1), 9; https://doi.org/10.3390/cells12010009 - 20 Dec 2022

Cited by 2 | Viewed by 1794

Abstract

The shape and load bearing strength of cells are determined by the complex protein network comprising the actin-myosin cytoskeleton [...] Full article

(This article belongs to the Special Issue Actin-Myosin Cytoskeleton Regulation and Function)

Research

Jump to: Editorial, Review, Other

20 pages, 2557 KiB

Open AccessArticle

Altered Expression Ratio of Actin-Binding Gelsolin Isoforms Is a Novel Hallmark of Mitochondrial OXPHOS Dysfunction

by Alberto García-Bartolomé, Ana Peñas, María Illescas, Verónica Bermejo, Sandra López-Calcerrada, Rafael Pérez-Pérez, Lorena Marín-Buera, Cristina Domínguez-González, Joaquín Arenas, Miguel A. Martín and Cristina Ugalde

Cells 2020, 9(9), 1922; https://doi.org/10.3390/cells9091922 - 19 Aug 2020

Cited by 11 | Viewed by 2898

Abstract

Mitochondrial oxidative phosphorylation (OXPHOS) defects are the primary cause of inborn errors of energy metabolism. Despite considerable progress on their genetic basis, their global pathophysiological consequences remain undefined. Previous studies reported that OXPHOS dysfunction associated with complex III deficiency exacerbated the expression and [...] Read more.

Mitochondrial oxidative phosphorylation (OXPHOS) defects are the primary cause of inborn errors of energy metabolism. Despite considerable progress on their genetic basis, their global pathophysiological consequences remain undefined. Previous studies reported that OXPHOS dysfunction associated with complex III deficiency exacerbated the expression and mitochondrial location of cytoskeletal gelsolin (GSN) to promote cell survival responses. In humans, besides the cytosolic isoform, GSN presents a plasma isoform secreted to extracellular environments. We analyzed the interplay between both GSN isoforms in human cellular and clinical models of OXPHOS dysfunction. Regardless of its pathogenic origin, OXPHOS dysfunction induced the physiological upregulation of cytosolic GSN in the mitochondria (mGSN), in parallel with a significant downregulation of plasma GSN (pGSN) levels. Consequently, significantly high mGSN-to-pGSN ratios were associated with OXPHOS deficiency both in human cells and blood. In contrast, control cells subjected to hydrogen peroxide or staurosporine treatments showed no correlation between oxidative stress or cell death induction and the altered levels and subcellular location of GSN isoforms, suggesting their specificity for OXPHOS dysfunction. In conclusion, a high mitochondrial-to-plasma GSN ratio represents a useful cellular indicator of OXPHOS defects, with potential use for future research of a wide range of clinical conditions with mitochondrial involvement. Full article

(This article belongs to the Special Issue Actin-Myosin Cytoskeleton Regulation and Function)

► Show Figures

Graphical abstract

15 pages, 5521 KiB

Open AccessArticle

Formation of Aberrant Myotubes by Myoblasts Lacking Myosin VI Is Associated with Alterations in the Cytoskeleton Organization, Myoblast Adhesion and Fusion

by Lilya Lehka, Małgorzata Topolewska, Dominika Wojton, Olena Karatsai, Paloma Alvarez-Suarez, Paweł Pomorski and Maria Jolanta Rędowicz

Cells 2020, 9(7), 1673; https://doi.org/10.3390/cells9071673 - 11 Jul 2020

Cited by 6 | Viewed by 4774

Abstract

We have previously postulated that unconventional myosin VI (MVI) could be involved in myoblast differentiation. Here, we addressed the mechanism(s) of its involvement using primary myoblast culture derived from the hindlimb muscles of Snell’s waltzer mice, the natural MVI knockouts (MVI-KO). We observed [...] Read more.

We have previously postulated that unconventional myosin VI (MVI) could be involved in myoblast differentiation. Here, we addressed the mechanism(s) of its involvement using primary myoblast culture derived from the hindlimb muscles of Snell’s waltzer mice, the natural MVI knockouts (MVI-KO). We observed that MVI-KO myotubes were formed faster than control heterozygous myoblasts (MVI-WT), with a three-fold increase in the number of myosac-like myotubes with centrally positioned nuclei. There were also changes in the levels of the myogenic transcription factors Pax7, MyoD and myogenin. This was accompanied by changes in the actin cytoskeleton and adhesive structure organization. We observed significant decreases in the levels of proteins involved in focal contact formation, such as talin and focal adhesion kinase (FAK). Interestingly, the levels of proteins involved in intercellular communication, M-cadherin and drebrin, were also affected. Furthermore, time-dependent alterations in the levels of the key proteins for myoblast membrane fusion, myomaker and myomerger, without effect on their cellular localization, were observed. Our data indicate that in the absence of MVI, the mechanisms controlling cytoskeleton organization, as well as myoblast adhesion and fusion, are dysregulated, leading to the formation of aberrant myotubes. Full article

(This article belongs to the Special Issue Actin-Myosin Cytoskeleton Regulation and Function)

► Show Figures

Figure 1

22 pages, 6927 KiB

Open AccessArticle

The WAVE Regulatory Complex Is Required to Balance Protrusion and Adhesion in Migration

by Jamie A. Whitelaw, Karthic Swaminathan, Frieda Kage and Laura M. Machesky

Cells 2020, 9(7), 1635; https://doi.org/10.3390/cells9071635 - 7 Jul 2020

Cited by 19 | Viewed by 4901

Abstract

Cells migrating over 2D substrates are required to polymerise actin at the leading edge to form lamellipodia protrusions and nascent adhesions to anchor the protrusion to the substrate. The major actin nucleator in lamellipodia formation is the Arp2/3 complex, which is activated by [...] Read more.

Cells migrating over 2D substrates are required to polymerise actin at the leading edge to form lamellipodia protrusions and nascent adhesions to anchor the protrusion to the substrate. The major actin nucleator in lamellipodia formation is the Arp2/3 complex, which is activated by the WAVE regulatory complex (WRC). Using inducible Nckap1 floxed mouse embryonic fibroblasts (MEFs), we confirm that the WRC is required for lamellipodia formation, and importantly, for generating the retrograde flow of actin from the leading cell edge. The loss of NCKAP1 also affects cell spreading and focal adhesion dynamics. In the absence of lamellipodium, cells can become elongated and move with a single thin pseudopod, which appears devoid of N-WASP. This phenotype was more prevalent on collagen than fibronectin, where we observed an increase in migratory speed. Thus, 2D cell migration on collagen is less dependent on branched actin. Full article

(This article belongs to the Special Issue Actin-Myosin Cytoskeleton Regulation and Function)

► Show Figures

Figure 1

14 pages, 2930 KiB

Open AccessArticle

Molecular Dissection of Neurodevelopmental Disorder-Causing Mutations in CYFIP2

by Matthias Schaks, Michael Reinke, Walter Witke and Klemens Rottner

Cells 2020, 9(6), 1355; https://doi.org/10.3390/cells9061355 - 29 May 2020

Cited by 15 | Viewed by 3631

Abstract

Actin remodeling is frequently regulated by antagonistic activities driving protrusion and contraction downstream of Rac and Rho small GTPases, respectively. WAVE regulatory complex (WRC), which primarily operates downstream of Rac, plays pivotal roles in neuronal morphogenesis. Recently, two independent studies described de novo [...] Read more.

Actin remodeling is frequently regulated by antagonistic activities driving protrusion and contraction downstream of Rac and Rho small GTPases, respectively. WAVE regulatory complex (WRC), which primarily operates downstream of Rac, plays pivotal roles in neuronal morphogenesis. Recently, two independent studies described de novo mutations in the CYFIP2 subunit of WRC, which caused intellectual disability (ID) in humans. Although mutations had been proposed to effect WRC activation, no experimental evidence for this was provided. Here, we made use of CRISPR/Cas9-engineered B16-F1 cell lines that were reconstituted with ID-causing CYFIP variants in different experimental contexts. Almost all CYFIP2-derived mutations (7 out of 8) promoted WRC activation, but to variable extent and with at least two independent mechanisms. The majority of mutations occurs in a conserved WAVE-binding region, required for WRC transinhibition. One mutation is positioned closely adjacent to the Rac-binding A site and appears to ease Rac-mediated WRC activation. As opposed to these gain-of-function mutations, a truncating mutant represented a loss-of-function variant and failed to interact with WRC components. Collectively, our data show that explored CYFIP2 mutations frequently, but not always, coincide with WRC activation and suggest that normal brain development requires a delicate and precisely tuned balance of neuronal WRC activity. Full article

(This article belongs to the Special Issue Actin-Myosin Cytoskeleton Regulation and Function)

► Show Figures

Graphical abstract

Review

Jump to: Editorial, Research, Other

14 pages, 1614 KiB

Open AccessReview

Actomyosin Contractility in the Generation and Plasticity of Axons and Dendritic Spines

by Marina Mikhaylova, Jakob Rentsch and Helge Ewers

Cells 2020, 9(9), 2006; https://doi.org/10.3390/cells9092006 - 1 Sep 2020

Cited by 10 | Viewed by 4780

Abstract

Actin and non-muscle myosins have long been known to play important roles in growth cone steering and neurite outgrowth. More recently, novel functions for non-muscle myosin have been described in axons and dendritic spines. Consequently, possible roles of actomyosin contraction in organizing and [...] Read more.

Actin and non-muscle myosins have long been known to play important roles in growth cone steering and neurite outgrowth. More recently, novel functions for non-muscle myosin have been described in axons and dendritic spines. Consequently, possible roles of actomyosin contraction in organizing and maintaining structural properties of dendritic spines, the size and location of axon initial segment and axonal diameter are emerging research topics. In this review, we aim to summarize recent findings involving myosin localization and function in these compartments and to discuss possible roles for actomyosin in their function and the signaling pathways that control them. Full article

(This article belongs to the Special Issue Actin-Myosin Cytoskeleton Regulation and Function)

► Show Figures

Figure 1

17 pages, 1664 KiB

Open AccessReview

Non-Muscle Myosin II in Axonal Cell Biology: From the Growth Cone to the Axon Initial Segment

by Ana Rita Costa and Monica M. Sousa

Cells 2020, 9(9), 1961; https://doi.org/10.3390/cells9091961 - 26 Aug 2020

Cited by 17 | Viewed by 5666

Abstract

By binding to actin filaments, non-muscle myosin II (NMII) generates actomyosin networks that hold unique contractile properties. Their dynamic nature is essential for neuronal biology including the establishment of polarity, growth cone formation and motility, axon growth during development (and axon regeneration in [...] Read more.

By binding to actin filaments, non-muscle myosin II (NMII) generates actomyosin networks that hold unique contractile properties. Their dynamic nature is essential for neuronal biology including the establishment of polarity, growth cone formation and motility, axon growth during development (and axon regeneration in the adult), radial and longitudinal axonal tension, and synapse formation and function. In this review, we discuss the current knowledge on the spatial distribution and function of the actomyosin cytoskeleton in different axonal compartments. We highlight some of the apparent contradictions and open questions in the field, including the role of NMII in the regulation of axon growth and regeneration, the possibility that NMII structural arrangement along the axon shaft may control both radial and longitudinal contractility, and the mechanism and functional purpose underlying NMII enrichment in the axon initial segment. With the advances in live cell imaging and super resolution microscopy, it is expected that in the near future the spatial distribution of NMII in the axon, and the mechanisms by which it participates in axonal biology will be further untangled. Full article

(This article belongs to the Special Issue Actin-Myosin Cytoskeleton Regulation and Function)

► Show Figures

Figure 1

29 pages, 1789 KiB

Open AccessReview

Conventional and Non-Conventional Roles of Non-Muscle Myosin II-Actin in Neuronal Development and Degeneration

by Míriam Javier-Torrent and Carlos A. Saura

Cells 2020, 9(9), 1926; https://doi.org/10.3390/cells9091926 - 19 Aug 2020

Cited by 15 | Viewed by 6126

Abstract

Myosins are motor proteins that use chemical energy to produce mechanical forces driving actin cytoskeletal dynamics. In the brain, the conventional non-muscle myosin II (NMII) regulates actin filament cytoskeletal assembly and contractile forces during structural remodeling of axons and dendrites, contributing to morphology, [...] Read more.

Myosins are motor proteins that use chemical energy to produce mechanical forces driving actin cytoskeletal dynamics. In the brain, the conventional non-muscle myosin II (NMII) regulates actin filament cytoskeletal assembly and contractile forces during structural remodeling of axons and dendrites, contributing to morphology, polarization, and migration of neurons during brain development. NMII isoforms also participate in neurotransmission and synaptic plasticity by driving actin cytoskeletal dynamics during synaptic vesicle release and retrieval, and formation, maturation, and remodeling of dendritic spines. NMIIs are expressed differentially in cerebral non-neuronal cells, such as microglia, astrocytes, and endothelial cells, wherein they play key functions in inflammation, myelination, and repair. Besides major efforts to understand the physiological functions and regulatory mechanisms of NMIIs in the nervous system, their contributions to brain pathologies are still largely unclear. Nonetheless, genetic mutations or deregulation of NMII and its regulatory effectors are linked to autism, schizophrenia, intellectual disability, and neurodegeneration, indicating non-conventional roles of NMIIs in cellular mechanisms underlying neurodevelopmental and neurodegenerative disorders. Here, we summarize the emerging biological roles of NMIIs in the brain, and discuss how actomyosin signaling contributes to dysfunction of neurons and glial cells in the context of neurological disorders. This knowledge is relevant for a deep understanding of NMIIs on the pathogenesis and therapeutics of neuropsychiatric and neurodegenerative diseases. Full article

(This article belongs to the Special Issue Actin-Myosin Cytoskeleton Regulation and Function)

► Show Figures

Figure 1

15 pages, 2025 KiB

Open AccessReview

Myosin XVI in the Nervous System

by Elek Telek, András Kengyel and Beáta Bugyi

Cells 2020, 9(8), 1903; https://doi.org/10.3390/cells9081903 - 15 Aug 2020

Cited by 6 | Viewed by 3787

Abstract

The myosin family is a large inventory of actin-associated motor proteins that participate in a diverse array of cellular functions. Several myosin classes are expressed in neural cells and play important roles in neural functioning. A recently discovered member of the myosin superfamily, [...] Read more.

The myosin family is a large inventory of actin-associated motor proteins that participate in a diverse array of cellular functions. Several myosin classes are expressed in neural cells and play important roles in neural functioning. A recently discovered member of the myosin superfamily, the vertebrate-specific myosin XVI (Myo16) class is expressed predominantly in neural tissues and appears to be involved in the development and proper functioning of the nervous system. Accordingly, the alterations of MYO16 has been linked to neurological disorders. Although the role of Myo16 as a generic actin-associated motor is still enigmatic, the N-, and C-terminal extensions that flank the motor domain seem to confer unique structural features and versatile interactions to the protein. Recent biochemical and physiological examinations portray Myo16 as a signal transduction element that integrates cell signaling pathways to actin cytoskeleton reorganization. This review discusses the current knowledge of the structure-function relation of Myo16. In light of its prevalent localization, the emphasis is laid on the neural aspects. Full article

(This article belongs to the Special Issue Actin-Myosin Cytoskeleton Regulation and Function)

► Show Figures

Figure 1

27 pages, 933 KiB

Open AccessReview

Regulation of the Actin Cytoskeleton in Podocytes

by Judith Blaine and James Dylewski

Cells 2020, 9(7), 1700; https://doi.org/10.3390/cells9071700 - 16 Jul 2020

Cited by 74 | Viewed by 9876

Abstract

Podocytes are an integral part of the glomerular filtration barrier, a structure that prevents filtration of large proteins and macromolecules into the urine. Podocyte function is dependent on actin cytoskeleton regulation within the foot processes, structures that link podocytes to the glomerular basement [...] Read more.

Podocytes are an integral part of the glomerular filtration barrier, a structure that prevents filtration of large proteins and macromolecules into the urine. Podocyte function is dependent on actin cytoskeleton regulation within the foot processes, structures that link podocytes to the glomerular basement membrane. Actin cytoskeleton dynamics in podocyte foot processes are complex and regulated by multiple proteins and other factors. There are two key signal integration and structural hubs within foot processes that regulate the actin cytoskeleton: the slit diaphragm and focal adhesions. Both modulate actin filament extension as well as foot process mobility. No matter what the initial cause, the final common pathway of podocyte damage is dysregulation of the actin cytoskeleton leading to foot process retraction and proteinuria. Disruption of the actin cytoskeleton can be due to acquired causes or to genetic mutations in key actin regulatory and signaling proteins. Here, we describe the major structural and signaling components that regulate the actin cytoskeleton in podocytes as well as acquired and genetic causes of actin dysregulation. Full article

(This article belongs to the Special Issue Actin-Myosin Cytoskeleton Regulation and Function)

► Show Figures

Figure 1

31 pages, 2122 KiB

Open AccessReview

MicroRNA Regulatory Pathways in the Control of the Actin–Myosin Cytoskeleton

by Karen Uray, Evelin Major and Beata Lontay

Cells 2020, 9(7), 1649; https://doi.org/10.3390/cells9071649 - 9 Jul 2020

Cited by 16 | Viewed by 5286

Abstract

MicroRNAs (miRNAs) are key modulators of post-transcriptional gene regulation in a plethora of processes, including actin–myosin cytoskeleton dynamics. Recent evidence points to the widespread effects of miRNAs on actin–myosin cytoskeleton dynamics, either directly on the expression of actin and myosin genes or indirectly [...] Read more.

MicroRNAs (miRNAs) are key modulators of post-transcriptional gene regulation in a plethora of processes, including actin–myosin cytoskeleton dynamics. Recent evidence points to the widespread effects of miRNAs on actin–myosin cytoskeleton dynamics, either directly on the expression of actin and myosin genes or indirectly on the diverse signaling cascades modulating cytoskeletal arrangement. Furthermore, studies from various human models indicate that miRNAs contribute to the development of various human disorders. The potentially huge impact of miRNA-based mechanisms on cytoskeletal elements is just starting to be recognized. In this review, we summarize recent knowledge about the importance of microRNA modulation of the actin–myosin cytoskeleton affecting physiological processes, including cardiovascular function, hematopoiesis, podocyte physiology, and osteogenesis. Full article

(This article belongs to the Special Issue Actin-Myosin Cytoskeleton Regulation and Function)

► Show Figures

Figure 1

24 pages, 3092 KiB

Open AccessReview

Non-Muscle Myosin 2A (NM2A): Structure, Regulation and Function

by Cláudia Brito and Sandra Sousa

Cells 2020, 9(7), 1590; https://doi.org/10.3390/cells9071590 - 1 Jul 2020

Cited by 44 | Viewed by 10008

Abstract

Non-muscle myosin 2A (NM2A) is a motor cytoskeletal enzyme with crucial importance from the early stages of development until adulthood. Due to its capacity to convert chemical energy into force, NM2A powers the contraction of the actomyosin cytoskeleton, required for proper cell division, [...] Read more.

Non-muscle myosin 2A (NM2A) is a motor cytoskeletal enzyme with crucial importance from the early stages of development until adulthood. Due to its capacity to convert chemical energy into force, NM2A powers the contraction of the actomyosin cytoskeleton, required for proper cell division, adhesion and migration, among other cellular functions. Although NM2A has been extensively studied, new findings revealed that a lot remains to be discovered concerning its spatiotemporal regulation in the intracellular environment. In recent years, new functions were attributed to NM2A and its activity was associated to a plethora of illnesses, including neurological disorders and infectious diseases. Here, we provide a concise overview on the current knowledge regarding the structure, the function and the regulation of NM2A. In addition, we recapitulate NM2A-associated diseases and discuss its potential as a therapeutic target. Full article

(This article belongs to the Special Issue Actin-Myosin Cytoskeleton Regulation and Function)

► Show Figures

Figure 1

20 pages, 952 KiB

Open AccessReview

Huntington’s Disease—An Outlook on the Interplay of the HTT Protein, Microtubules and Actin Cytoskeletal Components

by Aleksandra S. Taran, Lilia D. Shuvalova, Maria A. Lagarkova and Irina B. Alieva

Cells 2020, 9(6), 1514; https://doi.org/10.3390/cells9061514 - 22 Jun 2020

Cited by 19 | Viewed by 5400

Abstract

Huntington’s disease is a severe and currently incurable neurodegenerative disease. An autosomal dominant mutation in the Huntingtin gene (HTT) causes an increase in the polyglutamine fragment length at the protein N-terminus. The consequence of the mutation is the death of neurons, [...] Read more.

Huntington’s disease is a severe and currently incurable neurodegenerative disease. An autosomal dominant mutation in the Huntingtin gene (HTT) causes an increase in the polyglutamine fragment length at the protein N-terminus. The consequence of the mutation is the death of neurons, mostly striatal neurons, leading to the occurrence of a complex of motor, cognitive and emotional-volitional personality sphere disorders in carriers. Despite intensive studies, the functions of both mutant and wild-type huntingtin remain poorly understood. Surprisingly, there is the selective effect of the mutant form of HTT even on nervous tissue, whereas the protein is expressed ubiquitously. Huntingtin plays a role in cell physiology and affects cell transport, endocytosis, protein degradation and other cellular and molecular processes. Our experimental data mining let us conclude that a significant part of the Huntingtin-involved cellular processes is mediated by microtubules and other cytoskeletal cell structures. The review attempts to look at unresolved issues in the study of the huntingtin and its mutant form, including their functions affecting microtubules and other components of the cell cytoskeleton. Full article

(This article belongs to the Special Issue Actin-Myosin Cytoskeleton Regulation and Function)

► Show Figures

Figure 1

21 pages, 2613 KiB

Open AccessFeature PaperReview

Linking the Landscape of MYH9-Related Diseases to the Molecular Mechanisms that Control Non-Muscle Myosin II-A Function in Cells

by Gloria Asensio-Juárez, Clara Llorente-González and Miguel Vicente-Manzanares

Cells 2020, 9(6), 1458; https://doi.org/10.3390/cells9061458 - 12 Jun 2020

Cited by 44 | Viewed by 7318

Abstract

The MYH9 gene encodes the heavy chain (MHCII) of non-muscle myosin II A (NMII-A). This is an actin-binding molecular motor essential for development that participates in many crucial cellular processes such as adhesion, cell migration, cytokinesis and polarization, maintenance of cell shape and [...] Read more.

The MYH9 gene encodes the heavy chain (MHCII) of non-muscle myosin II A (NMII-A). This is an actin-binding molecular motor essential for development that participates in many crucial cellular processes such as adhesion, cell migration, cytokinesis and polarization, maintenance of cell shape and signal transduction. Several types of mutations in the MYH9 gene cause an array of autosomal dominant disorders, globally known as MYH9-related diseases (MYH9-RD). These include May-Hegglin anomaly (MHA), Epstein syndrome (EPS), Fechtner syndrome (FTS) and Sebastian platelet syndrome (SPS). Although caused by different MYH9 mutations, all patients present macrothrombocytopenia, but may later display other pathologies, including loss of hearing, renal failure and presenile cataracts. The correlation between the molecular and cellular effects of the different mutations and clinical presentation are beginning to be established. In this review, we correlate the defects that MYH9 mutations cause at a molecular and cellular level (for example, deficient filament formation, altered ATPase activity or actin-binding) with the clinical presentation of the syndromes in human patients. We address why these syndromes are tissue restricted, and the existence of possible compensatory mechanisms, including residual activity of mutant NMII-A and/or the formation of heteropolymers or co-polymers with other NMII isoforms. Full article

(This article belongs to the Special Issue Actin-Myosin Cytoskeleton Regulation and Function)

► Show Figures

Figure 1

19 pages, 683 KiB

Open AccessReview

Actin and Myosin in Non-Neuronal Exocytosis

by Pika Miklavc and Manfred Frick

Cells 2020, 9(6), 1455; https://doi.org/10.3390/cells9061455 - 11 Jun 2020

Cited by 25 | Viewed by 7042

Abstract

Cellular secretion depends on exocytosis of secretory vesicles and discharge of vesicle contents. Actin and myosin are essential for pre-fusion and post-fusion stages of exocytosis. Secretory vesicles depend on actin for transport to and attachment at the cell cortex during the pre-fusion phase. [...] Read more.

Cellular secretion depends on exocytosis of secretory vesicles and discharge of vesicle contents. Actin and myosin are essential for pre-fusion and post-fusion stages of exocytosis. Secretory vesicles depend on actin for transport to and attachment at the cell cortex during the pre-fusion phase. Actin coats on fused vesicles contribute to stabilization of large vesicles, active vesicle contraction and/or retrieval of excess membrane during the post-fusion phase. Myosin molecular motors complement the role of actin. Myosin V is required for vesicle trafficking and attachment to cortical actin. Myosin I and II members engage in local remodeling of cortical actin to allow vesicles to get access to the plasma membrane for membrane fusion. Myosins stabilize open fusion pores and contribute to anchoring and contraction of actin coats to facilitate vesicle content release. Actin and myosin function in secretion is regulated by a plethora of interacting regulatory lipids and proteins. Some of these processes have been first described in non-neuronal cells and reflect adaptations to exocytosis of large secretory vesicles and/or secretion of bulky vesicle cargoes. Here we collate the current knowledge and highlight the role of actomyosin during distinct phases of exocytosis in an attempt to identify unifying molecular mechanisms in non-neuronal secretory cells. Full article

(This article belongs to the Special Issue Actin-Myosin Cytoskeleton Regulation and Function)

► Show Figures

Figure 1

Other

Jump to: Editorial, Research, Review

11 pages, 2313 KiB

Open AccessPerspective

Kinase-Independent Functions of MASTL in Cancer: A New Perspective on MASTL Targeting

by James Ronald William Conway, Elisa Närvä, Maria Emilia Taskinen and Johanna Ivaska

Cells 2020, 9(7), 1624; https://doi.org/10.3390/cells9071624 - 6 Jul 2020

Cited by 4 | Viewed by 3571

Abstract

Microtubule-associated serine/threonine kinase-like (MASTL; Greatwall) is a well-characterized kinase, whose catalytic role has been extensively studied in relation to cell-cycle acceleration. Importantly, MASTL has been implicated to play a substantial role in cancer progression and subsequent studies have shown that MASTL is a [...] Read more.

Microtubule-associated serine/threonine kinase-like (MASTL; Greatwall) is a well-characterized kinase, whose catalytic role has been extensively studied in relation to cell-cycle acceleration. Importantly, MASTL has been implicated to play a substantial role in cancer progression and subsequent studies have shown that MASTL is a significant regulator of the cellular actomyosin cytoskeleton. Several kinases have non-catalytic properties, which are essential or even sufficient for their functions. Likewise, MASTL functions have been attributed both to kinase-dependent phosphorylation of downstream substrates, but also to kinase-independent regulation of the actomyosin contractile machinery. In this review, we aimed to highlight the catalytic and non-catalytic roles of MASTL in proliferation, migration, and invasion. Further, we discussed the implications of this dual role for therapeutic design. Full article

(This article belongs to the Special Issue Actin-Myosin Cytoskeleton Regulation and Function)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Actin-Myosin Cytoskeleton Regulation and Function

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Related Special Issue

Published Papers (16 papers)

Editorial

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI