scholarly journals Cortactin signalling and dynamic actin networks

2004 ◽  
Vol 382 (1) ◽  
pp. 13-25 ◽  
Author(s):  
Roger J. DALY
Keyword(s):  
Tyrosine Kinase ◽  
Actin Cytoskeleton ◽  
Current Knowledge ◽  
Actin Binding ◽  
Related Protein ◽  
Protein Targets ◽  
Actin Networks ◽  
Multiple Protein ◽  
Initial Characterization

Cortactin was first identified over a decade ago, and its initial characterization as both an F-actin binding protein and v-Src substrate suggested that it was likely to be a key regulator of actin rearrangements in response to tyrosine kinase signalling. The recent discovery that cortactin binds and activates the actin related protein (Arp)2/3 complex, and thus regulates the formation of branched actin networks, together with the identification of multiple protein targets of the cortactin SH3 domain, have revealed diverse cellular roles for this protein. This article reviews current knowledge regarding the role of cortactin in signalling to the actin cytoskeleton in the context of these developments.

scholarly journals Bundling up the Role of the Actin Cytoskeleton in Primary Root Growth

2021 ◽  
Vol 12 ◽  
Author(s):  
Judith García-González ◽  
Kasper van Gelderen
Keyword(s):  
Root Growth ◽  
Actin Cytoskeleton ◽  
Cell Elongation ◽  
Feedback Loop ◽  
Primary Root ◽  
Actin Binding ◽  
Actin Network ◽  
Actin Organization ◽  
Primary Root Growth

Primary root growth is required by the plant to anchor in the soil and reach out for nutrients and water, while dealing with obstacles. Efficient root elongation and bending depends upon the coordinated action of environmental sensing, signal transduction, and growth responses. The actin cytoskeleton is a highly plastic network that constitutes a point of integration for environmental stimuli and hormonal pathways. In this review, we present a detailed compilation highlighting the importance of the actin cytoskeleton during primary root growth and we describe how actin-binding proteins, plant hormones, and actin-disrupting drugs affect root growth and root actin. We also discuss the feedback loop between actin and root responses to light and gravity. Actin affects cell division and elongation through the control of its own organization. We remark upon the importance of longitudinally oriented actin bundles as a hallmark of cell elongation as well as the role of the actin cytoskeleton in protein trafficking and vacuolar reshaping during this process. The actin network is shaped by a plethora of actin-binding proteins; however, there is still a large gap in connecting the molecular function of these proteins with their developmental effects. Here, we summarize their function and known effects on primary root growth with a focus on their high level of specialization. Light and gravity are key factors that help us understand root growth directionality. The response of the root to gravity relies on hormonal, particularly auxin, homeostasis, and the actin cytoskeleton. Actin is necessary for the perception of the gravity stimulus via the repositioning of sedimenting statoliths, but it is also involved in mediating the growth response via the trafficking of auxin transporters and cell elongation. Furthermore, auxin and auxin analogs can affect the composition of the actin network, indicating a potential feedback loop. Light, in its turn, affects actin organization and hence, root growth, although its precise role remains largely unknown. Recently, fundamental studies with the latest techniques have given us more in-depth knowledge of the role and organization of actin in the coordination of root growth; however, there remains a lot to discover, especially in how actin organization helps cell shaping, and therefore root growth.

scholarly journals Modulation of the F-actin cytoskeleton by c-Abl tyrosine kinase in cell spreading and neurite extension

2002 ◽  
Vol 156 (5) ◽  
pp. 879-892 ◽  
Author(s):  
Pamela J. Woodring ◽  
E. David Litwack ◽  
Dennis D.M. O'Leary ◽  
Ginger R. Lucero ◽  
Jean Y.J. Wang ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Actin Cytoskeleton ◽  
Cortical Neurons ◽  
Cell Attachment ◽  
Actin Binding ◽  
Src Tyrosine Kinase ◽  
Reciprocal Regulation ◽  
Nonreceptor Tyrosine Kinase ◽  
Abl Tyrosine Kinase ◽  
Cytoskeleton Dynamics

The nonreceptor tyrosine kinase encoded by the c-Abl gene has the unique feature of an F-actin binding domain (FABD). Purified c-Abl tyrosine kinase is inhibited by F-actin, and this inhibition can be relieved through mutation of its FABD. The c-Abl kinase is activated by physiological signals that also regulate the actin cytoskeleton. We show here that c-Abl stimulated the formation of actin microspikes in fibroblasts spreading on fibronectin. This function of c-Abl is dependent on kinase activity and is not shared by c-Src tyrosine kinase. The Abl-dependent F-actin microspikes occurred under conditions where the Rho-family GTPases were inhibited. The FABD-mutated c-Abl, which is active in detached fibroblasts, stimulated F-actin microspikes independent of cell attachment. Moreover, FABD-mutated c-Abl stimulated the formation of F-actin branches in neurites of rat embryonic cortical neurons. The reciprocal regulation between F-actin and the c-Abl tyrosine kinase may provide a self-limiting mechanism in the control of actin cytoskeleton dynamics.

scholarly journals The Saccharomyces cerevisiae actin-related protein Arp2 is involved in the actin cytoskeleton.

1996 ◽  
Vol 134 (1) ◽  
pp. 117-132 ◽  
Author(s):  
V Moreau ◽  
A Madania ◽  
R P Martin ◽  
B Winson
Keyword(s):  
Actin Cytoskeleton ◽  
Genetic Interaction ◽  
Lucifer Yellow ◽  
Temperature Sensitive ◽  
Related Protein ◽  
Gene Encoding ◽  
Membrane Growth ◽  
Mutant Phenotypes ◽  
Mutant Cells

Arp2p is an essential yeast actin-related protein. Disruption of the corresponding ARP2 gene leads to a terminal phenotype characterized by the presence of a single large bud. Thus, Arp2p may be important for a late stage of the cell cycle (Schwob, E., and R.P. Martin, 1992. Nature (Lond.). 355:179-182). We have localized Arp2p by indirect immunofluorescence. Specific peptide antibodies revealed punctate staining under the plasma membrane, which partially colocalizes with actin. Temperature-sensitive arp2 mutations were created by PCR mutagenesis and selected by an ade2/SUP11 sectoring screen. One temperature-sensitive mutant that was characterized, arp2-H330L, was osmosensitive and had an altered actin cytoskeleton at a nonpermissive temperature, suggesting a role of Arp2p in the actin cytoskeleton. Random budding patterns were observed in both haploid and diploid arp2-H330L mutant cells. Endocytosis, as judged by Lucifer yellow uptake, was severely reduced in the mutant, at all temperatures. In addition, genetic interaction was observed between temperature-sensitive alleles arp2-H330L and cdc10-1. CDC10 is a gene encoding a neck filament-associated protein that is necessary for polarized growth and cytokinesis. Overall, the immunolocalization, mutant phenotypes, and genetic interaction suggest that the Arp2 protein is an essential component of the actin cytoskeleton that is involved in membrane growth and polarity, as well as in endocytosis.

scholarly journals The role of profilin-1 in cardiovascular diseases

2021 ◽  
Vol 134 (9) ◽  
Author(s):  
Abigail Allen ◽  
David Gau ◽  
Partha Roy
Keyword(s):  
Cardiovascular Diseases ◽  
Actin Cytoskeleton ◽  
Cell Cycle Progression ◽  
Neurological Diseases ◽  
Essential Feature ◽  
Actin Binding ◽  
Cycle Progression ◽  
Cellular Processes ◽  
Damage Response

ABSTRACT Dynamic remodeling of the actin cytoskeleton is an essential feature for virtually all actin-dependent cellular processes, including cell migration, cell cycle progression, chromatin remodeling and gene expression, and even the DNA damage response. An altered actin cytoskeleton is a structural hallmark associated with numerous pathologies ranging from cardiovascular diseases to immune disorders, neurological diseases and cancer. The actin cytoskeleton in cells is regulated through the orchestrated actions of a myriad of actin-binding proteins. In this Review, we provide a brief overview of the structure and functions of the actin-monomer-binding protein profilin-1 (Pfn1) and then discuss how dysregulated expression of Pfn1 contributes to diseases associated with the cardiovascular system.

scholarly journals ARP2/3-Mediated Actin Nucleation Associated With Symbiosome Membrane Is Essential for the Development of Symbiosomes in Infected Cells of Medicago truncatula Root Nodules

2015 ◽  
Vol 28 (5) ◽  
pp. 605-614 ◽  
Author(s):  
Aleksandr Gavrin ◽  
Veerle Jansen ◽  
Sergey Ivanov ◽  
Ton Bisseling ◽  
Elena Fedorova
Keyword(s):  
Actin Cytoskeleton ◽  
Host Cell ◽  
Medicago Truncatula ◽  
Root Nodules ◽  
Nitrogen Fixing ◽  
Actin Networks ◽  
Cell Plasma ◽  
Membrane Compartments ◽  
Infected Cells

The nitrogen-fixing rhizobia in the symbiotic infected cells of root nodules are kept in membrane compartments derived from the host cell plasma membrane, forming what are known as symbiosomes. These are maintained as individual units, with mature symbiosomes having a specific radial position in the host cell cytoplasm. The mechanisms that adapt the host cell architecture to accommodate intracellular bacteria are not clear. The intracellular organization of any cell depends heavily on the actin cytoskeleton. Dynamic rearrangement of the actin cytoskeleton is crucial for cytoplasm organization and intracellular trafficking of vesicles and organelles. A key component of the actin cytoskeleton rearrangement is the ARP2/3 complex, which nucleates new actin filaments and forms branched actin networks. To clarify the role of the ARP2/3 complex in the development of infected cells and symbiosomes, we analyzed the pattern of actin microfilaments and the functional role of ARP3 in Medicago truncatula root nodules. In infected cells, ARP3 protein and actin were spatially associated with maturing symbiosomes. Partial ARP3 silencing causes defects in symbiosome development; in particular, ARP3 silencing disrupts the final differentiation steps in functional maturation into nitrogen-fixing units.

scholarly journals The C-terminal tail domain of metavinculin, vinculin’s splice variant, severs actin filaments

2012 ◽  
Vol 197 (5) ◽  
pp. 585-593 ◽  
Author(s):  
Mandy E.W. Janssen ◽  
HongJun Liu ◽  
Niels Volkmann ◽  
Dorit Hanein
Keyword(s):  
Actin Filaments ◽  
Splice Variant ◽  
Point Mutations ◽  
Actin Binding ◽  
Tail Domain ◽  
Protein Assemblies ◽  
Multiple Protein ◽  
External Forces ◽  
Actin Binding Site

Vinculin and its splice variant, metavinculin (MV), are key elements of multiple protein assemblies linking the extracellular matrix to the actin cytoskeleton. Vinculin is expressed ubiquitously, whereas MV is mainly expressed in smooth and cardiac muscle tissue. The only difference in amino acid sequence between the isoforms is a 68-residue insert in the C-terminal tail domain of MV (MVt). Although the functional role of this insert remains elusive, its importance is exemplified by point mutations that are associated with dilated and hypertrophic cardiomyopathy. In vinculin, the actin binding site resides in the tail domain. In this paper, we show that MVt binds actin filaments similarly to the vinculin tail domain. Unlike its splice variant, MVt did not bundle actin filaments. Instead, MVt promoted severing of actin filaments, most efficiently at substoichiometric concentrations. This surprising and seemingly contradictory alteration of vinculin function by the 68-residue insert may be essential for modulating compliance of vinculin-induced actin bundles when exposed to rapidly increasing external forces.

The role of actin-binding proteins in the control of endothelial barrier integrity

2015 ◽  
Vol 113 (01) ◽  
pp. 20-36 ◽  
Author(s):  
Alexander García-Ponce ◽  
Alí Francisco Citalán-Madrid ◽  
Martha Velázquez-Avila ◽  
Hilda Vargas-Robles ◽  
Michael Schnoor
Keyword(s):  
Endothelial Cell ◽  
Actin Cytoskeleton ◽  
Vascular Permeability ◽  
Binding Proteins ◽  
Small Gtpases ◽  
Endothelial Barrier ◽  
Actin Binding ◽  
Actin Binding Proteins ◽  
Cell Contacts

SummaryThe endothelial barrier of the vasculature is of utmost importance for separating the blood stream from underlying tissues. This barrier is formed by tight and adherens junctions (TJ and AJ) that form intercellular endothelial contacts. TJ and AJ are integral membrane structures that are connected to the actin cytoskeleton via various adaptor molecules. Consequently, the actin cytoskeleton plays a crucial role in regulating the stability of endothelial cell contacts and vascular permeability. While a circumferential cortical actin ring stabilises junctions, the formation of contractile stress fibres, e. g. under inflammatory conditions, can contribute to junction destabilisation. However, the role of actin-binding proteins (ABP) in the control of vascular permeability has long been underestimated. Naturally, ABP regulate permeability via regulation of actin remodelling but some actin-binding molecules can also act independently of actin and control vascular permeability via various signalling mechanisms such as activation of small GTPases. Several studies have recently been published highlighting the importance of actin-binding molecules such as cortactin, ezrin/ radixin/moesin, Arp2/3, VASP or WASP for the control of vascular permeability by various mechanisms. These proteins have been described to regulate vascular permeability under various pathophysiological conditions and are thus of clinical relevance as targets for the development of treatment strategies for disorders that are characterised by vascular hyperpermeability such as sepsis. This review highlights recent advances in determining the role of ABP in the control of endothelial cell contacts and vascular permeability.

scholarly journals The emerging role of the KCTD proteins in cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Annapaola Angrisani ◽  
Annamaria Di Fiore ◽  
Enrico De Smaele ◽  
Marta Moretti
Keyword(s):  
Neurological Disorders ◽  
Current Knowledge ◽  
Family Members ◽  
Protein Targets ◽  
Cancer Hallmarks ◽  
Published Evidence ◽  
Oncogenic Pathways ◽  
Tetramerization Domain ◽  
Human Family

AbstractThe human family of Potassium (K+) Channel Tetramerization Domain (KCTD) proteins counts 25 members, and a significant number of them are still only partially characterized. While some of the KCTDs have been linked to neurological disorders or obesity, a growing tally of KCTDs are being associated with cancer hallmarks or involved in the modulation of specific oncogenic pathways. Indeed, the potential relevance of the variegate KCTD family in cancer warrants an updated picture of the current knowledge and highlights the need for further research on KCTD members as either putative therapeutic targets, or diagnostic/prognostic markers. Homology between family members, capability to participate in ubiquitination and degradation of different protein targets, ability to heterodimerize between members, role played in the main signalling pathways involved in development and cancer, are all factors that need to be considered in the search for new key players in tumorigenesis. In this review we summarize the recent published evidence on KCTD members’ involvement in cancer. Furthermore, by integrating this information with data extrapolated from public databases that suggest new potential associations with cancers, we hypothesize that the number of KCTD family members involved in tumorigenesis (either as positive or negative modulator) may be bigger than so far demonstrated.

scholarly journals Diversity from similarity: cellular strategies for assigning particular identities to actin filaments and networks

Open Biology ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 200157
Author(s):  
Micaela Boiero Sanders ◽  
Adrien Antkowiak ◽  
Alphée Michelot
Keyword(s):  
Mechanical Properties ◽  
Actin Cytoskeleton ◽  
Actin Filaments ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Competitive Binding ◽  
Actin Binding ◽  
Actin Isoforms ◽  
Actin Networks ◽  
Covalent Modifications

The actin cytoskeleton has the particularity of being assembled into many functionally distinct filamentous networks from a common reservoir of monomeric actin. Each of these networks has its own geometrical, dynamical and mechanical properties, because they are capable of recruiting specific families of actin-binding proteins (ABPs), while excluding the others. This review discusses our current understanding of the underlying molecular mechanisms that cells have developed over the course of evolution to segregate ABPs to appropriate actin networks. Segregation of ABPs requires the ability to distinguish actin networks as different substrates for ABPs, which is regulated in three different ways: (1) by the geometrical organization of actin filaments within networks, which promotes or inhibits the accumulation of ABPs; (2) by the identity of the networks' filaments, which results from the decoration of actin filaments with additional proteins such as tropomyosin, from the use of different actin isoforms or from covalent modifications of actin; (3) by the existence of collaborative or competitive binding to actin filaments between two or multiple ABPs. This review highlights that all these effects need to be taken into account to understand the proper localization of ABPs in cells, and discusses what remains to be understood in this field of research.

scholarly journals The molecular regulation of Janus kinase (JAK) activation

2014 ◽  
Vol 462 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Jeffrey J. Babon ◽  
Isabelle S. Lucet ◽  
James M. Murphy ◽  
Nicos A. Nicola ◽  
Leila N. Varghese
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Sh2 Domain ◽  
Janus Kinase ◽  
Causative Role ◽  
Tyrosine Kinase 2 ◽  
Src Homology

The JAK (Janus kinase) family members serve essential roles as the intracellular signalling effectors of cytokine receptors. This family, comprising JAK1, JAK2, JAK3 and TYK2 (tyrosine kinase 2), was first described more than 20 years ago, but the complexities underlying their activation, regulation and pleiotropic signalling functions are still being explored. Here, we review the current knowledge of their physiological functions and the causative role of activating and inactivating JAK mutations in human diseases, including haemopoietic malignancies, immunodeficiency and inflammatory diseases. At the molecular level, recent studies have greatly advanced our knowledge of the structures and organization of the component FERM (4.1/ezrin/radixin/moesin)-SH2 (Src homology 2), pseudokinase and kinase domains within the JAKs, the mechanism of JAK activation and, in particular, the role of the pseudokinase domain as a suppressor of the adjacent tyrosine kinase domain's catalytic activity. We also review recent advances in our understanding of the mechanisms of negative regulation exerted by the SH2 domain-containing proteins, SOCS (suppressors of cytokine signalling) proteins and LNK. These recent studies highlight the diversity of regulatory mechanisms utilized by the JAK family to maintain signalling fidelity, and suggest alternative therapeutic strategies to complement existing ATP-competitive kinase inhibitors.

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