Action of a 19K Protein from Porcine Brain on Actin Polymerization: A New Functional Class of Actin-Binding Proteins1

1984 ◽  
Vol 95 (2) ◽  
pp. 387-398 ◽  
Author(s):  
Eisuke NISHIDA ◽  
Shohei MAEKAWA ◽  
Eiro MUNEYUKI ◽  
Hikoichi SAKAI
Keyword(s):  
Actin Polymerization ◽  
Functional Class ◽  
Actin Binding ◽  
Porcine Brain

scholarly journals Macrolides: From Toxins to Therapeutics

Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 347
Author(s):  
Kiersten D. Lenz ◽  
Katja E. Klosterman ◽  
Harshini Mukundan ◽  
Jessica Z. Kubicek-Sutherland
Keyword(s):  
Actin Polymerization ◽  
Macrocyclic Lactone ◽  
Lactone Ring ◽  
Mechanisms Of Action ◽  
Functional Class ◽  
Actin Binding ◽  
Cellular Targets ◽  
Hydrophobic Compounds ◽  
Antibiotic Compounds ◽  
Therapeutic Properties

Macrolides are a diverse class of hydrophobic compounds characterized by a macrocyclic lactone ring and distinguished by variable side chains/groups. Some of the most well characterized macrolides are toxins produced by marine bacteria, sea sponges, and other species. Many marine macrolide toxins act as biomimetic molecules to natural actin-binding proteins, affecting actin polymerization, while other toxins act on different cytoskeletal components. The disruption of natural cytoskeletal processes affects cell motility and cytokinesis, and can result in cellular death. While many macrolides are toxic in nature, others have been shown to display therapeutic properties. Indeed, some of the most well known antibiotic compounds, including erythromycin, are macrolides. In addition to antibiotic properties, macrolides have been shown to display antiviral, antiparasitic, antifungal, and immunosuppressive actions. Here, we review each functional class of macrolides for their common structures, mechanisms of action, pharmacology, and human cellular targets.

scholarly journals Inhibition of actin polymerization by a synthetic dodecapeptide patterned on the sequence around the actin-binding site of cofilin

1991 ◽  
Vol 266 (16) ◽  
pp. 10485-10489
Author(s):  
N. Yonezawa ◽  
E. Nishida ◽  
K. Iida ◽  
H. Kumagai ◽  
I. Yahara ◽  
...  
Keyword(s):  
Binding Site ◽  
Actin Polymerization ◽  
Actin Binding ◽  
Actin Binding Site

scholarly journals Actin-binding protein promotes the bipolar and perpendicular branching of actin filaments.

1980 ◽  
Vol 87 (3) ◽  
pp. 841-848 ◽  
Author(s):  
J H Hartwig ◽  
J Tyler ◽  
T P Stossel
Keyword(s):  
Actin Filaments ◽  
Actin Polymerization ◽  
Average Length ◽  
Binding Protein ◽  
Actin Binding ◽  
Branch Points ◽  
Heavy Meromyosin ◽  
Actin Binding Protein ◽  
Protein Dimers ◽  
Protein Molecules

Branching filaments with striking perpendicularity form when actin polymerizes in the presence of macrophage actin-binding protein. Actin-binding protein molecules are visible at the branch points. Compared with actin polymerized in the absence of actin-binding proteins, not only do the filaments branch but the average length of the actin filaments decreases from 3.2 to 0.63 micrometer. Arrowhead complexes formed by addition of heavy meromyosin molecules to the branching actin filaments point toward the branch points. Actin-binding protein also accelerates the onset of actin polymerization. All of these findings show that actin filaments assemble from nucleating sites on actin-binding protein dimers. A branching polymerization of actin filaments from a preexisting lattice of actin filaments joined by actin-binding protein molecules could generate expansion of cortical cytoplasm in amoeboid cells.

scholarly journals Mechanisms responsible for F-actin stabilization after lysis of polymorphonuclear leukocytes.

1992 ◽  
Vol 116 (5) ◽  
pp. 1123-1134 ◽  
Author(s):  
M L Cano ◽  
L Cassimeris ◽  
M Fechheimer ◽  
S H Zigmond
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Actin Polymerization ◽  
Cell Movement ◽  
Actin Binding ◽  
Cross Linking ◽  
Macromolecular Complex ◽  
Actin Depolymerization ◽  
Gravitational Forces ◽  
End Capping

While actin polymerization and depolymerization are both essential for cell movement, few studies have focused on actin depolymerization. In vivo, depolymerization can occur exceedingly rapidly and in a spatially defined manner: the F-actin in the lamellipodia depolymerizes in 30 s after chemoattractant removal (Cassimeris, L., H. McNeill, and S. H. Zigmond. 1990. J. Cell Biol. 110:1067-1075). To begin to understand the regulation of F-actin depolymerization, we have examined F-actin depolymerization in lysates of polymorphonuclear leukocytes (PMNs). Surprisingly, much of the cell F-actin, measured with a TRITC-phalloidin-binding assay, was stable after lysis in a physiological salt buffer (0.15 M KCl): approximately 50% of the F-actin did not depolymerize even after 18 h. This stable F-actin included lamellar F-actin which could still be visualized one hour after lysis by staining with TRITC-phalloidin and by EM. We investigated the basis for this stability. In lysates with cell concentrations greater than 10(7) cells/ml, sufficient globular actin (G-actin) was present to result in a net increase in F-actin. However, the F-actin stability was not solely because of the presence of free G-actin since addition of DNase I to the lysate did not increase the F-actin loss. Nor did it appear to be because of barbed end capping factors since cell lysates provided sites for barbed end polymerization of exogenous added actin. The stable F-actin existed in a macromolecular complex that pelleted at low gravitational forces. Increasing the salt concentration of the lysis buffer decreased the amount of F-actin that pelleted at low gravitational forces and increased the amount of F-actin that depolymerized. Various actin-binding and cross-linking proteins such as tropomyosin, alpha-actinin, and actin-binding protein pelleted with the stable F-actin. In addition, we found that alpha-actinin, a filament cross-linking protein, inhibited the rate of pyrenyl F-actin depolymerization. These results suggested that actin cross-linking proteins may contribute to the stability of cellular actin after lysis. The activity of crosslinkers may be regulated in vivo to allow rapid turnover of lamellipodia F-actin.

scholarly journals Contribution of Filopodia to Cell Migration: A Mechanical Link between Protrusion and Contraction

2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Fei Xue ◽  
Deanna M. Janzen ◽  
David A. Knecht
Keyword(s):  
Cell Migration ◽  
Actin Polymerization ◽  
Myosin Ii ◽  
Temporal Distribution ◽  
Leading Edge ◽  
Distal Portion ◽  
Actin Binding ◽  
Actin Networks ◽  
Motile Cells ◽  
A Cell

Numerous F-actin containing structures are involved in regulating protrusion of membrane at the leading edge of motile cells. We have investigated the structure and dynamics of filopodia as they relate to events at the leading edge and the function of the trailing actin networks. We have found that although filopodia contain parallel bundles of actin, they contain a surprisingly nonuniform spatial and temporal distribution of actin binding proteins. Along the length of the actin filaments in a single filopodium, the most distal portion contains primarily T-plastin, while the proximal portion is primarily bound byα-actinin and coronin. Some filopodia are stationary, but lateral filopodia move with respect to the leading edge. They appear to form a mechanical link between the actin polymerization network at the front of the cell and the myosin motor activity in the cell body. The direction of lateral filopodial movement is associated with the direction of cell migration. When lateral filopodia initiate from and move toward only one side of a cell, the cell will turn opposite to the direction of filopodial flow. Therefore, this filopodia-myosin II system allows actin polymerization driven protrusion forces and myosin II mediated contractile force to be mechanically coordinated.

Distinct signals via Rho GTPases and Src drive shape changes by thrombin and sphingosine-1-phosphate in endothelial cells

2002 ◽  
Vol 115 (12) ◽  
pp. 2475-2484 ◽  
Author(s):  
Valérie Vouret-Craviari ◽  
Christine Bourcier ◽  
Etienne Boulter ◽  
Ellen Van Obberghen-Schilling
Keyword(s):  
Endothelial Cells ◽  
Rho Gtpases ◽  
Actin Polymerization ◽  
Morphological Changes ◽  
Umbilical Vein ◽  
Cell Spreading ◽  
Actin Binding ◽  
Sphingosine 1 Phosphate ◽  
And Migration ◽  
Umbilical Vein Endothelial Cells

Soluble mediators such as thrombin and sphingosine-1-phosphate regulate morphological changes in endothelial cells that affect vascular permeability and new blood vessel formation. Although these ligands activate a similar set of heterotrimeric G proteins, thrombin causes cell contraction and rounding whereas sphingosine-1-phosphate induces cell spreading and migration. A functional requirement for Rho family GTPases in the cytoskeletal responses to both ligands has been established, yet the dynamics of their regulation and additional signaling mechanisms that lead to such opposite effects remain poorly understood. Using a pull-down assay to monitor the activity of Rho GTPases in human umbilical vein endothelial cells, we find significant temporal and quantitative differences in RhoA and Rac1 activation. High levels of active RhoA rapidly accumulate in cells in response to thrombin whereas Rac1 is inhibited. In contrast, sphingosine-1-phosphate addition leads to comparatively weak and delayed activation of RhoA and it activates Rac1. In addition, we show here that sphingosine-1-phosphate treatment activates a Src family kinase and triggers recruitment of the F-actin-binding protein cortactin to sites of actin polymerization at the rim of membrane ruffles. Both Src and Rac pathways are essential for lamellipodia targeting of cortactin. Further, Src plays a determinant role in sphingosine-1-phosphate-induced cell spreading and migration. Taken together these data demonstrate that the thrombin-induced contractile and immobile phenotype in endothelial cells reflects both robust RhoA activation and Rac inhibition, whereas Src- and Rac-dependent events couple sphingosine-1-phosphate receptors to the actin polymerizing machinery that drives the extension of lamellipodia and cell migration.

scholarly journals Actin-binding Protein Drebrin Regulates HIV-1-triggered Actin Polymerization and Viral Infection

2013 ◽  
Vol 288 (39) ◽  
pp. 28382-28397 ◽  
Author(s):  
Mónica Gordón-Alonso ◽  
Vera Rocha-Perugini ◽  
Susana Álvarez ◽  
Ángeles Ursa ◽  
Nuria Izquierdo-Useros ◽  
...  
Keyword(s):  
Viral Infection ◽  
Actin Polymerization ◽  
Binding Protein ◽  
Actin Binding ◽  
Actin Binding Protein ◽  
Hiv 1

Abstract 20484: Enah/Vasp-Like Protein is a Critical Component in S1P-Mediated Endothelial Lamellipodia Formation

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Joseph B Mascarenhas ◽  
Ghassan Mouneimne ◽  
Carol C Gregorio ◽  
Mary E Brown ◽  
Ting Wang ◽  
...  
Keyword(s):  
Actin Polymerization ◽  
Human Lung ◽  
Actin Binding ◽  
Lipid Mediator ◽  
Dependent Manner ◽  
Cortical Actin ◽  
Pulmonary Endothelial Cells ◽  
Sphingosine 1 Phosphate ◽  
Barrier Regulation ◽  
Lamellipodia Formation

Ena/VASP like protein, or EVL, is an actin-binding protein that regulates cancer cell lamellipodia protrusive activity and cell motility via an actomyosin contractility-dependent mechanism. The function of EVL in human lung endothelial cell (EC) barrier regulation, especially by the endogenous bioactive lipid mediator sphingosine-1-phosphate (S1P), is largely unknown. In this current study, we demonstrated that EVL is an active component in S1P-mediated EC barrier enhancement and lamellipodia formation. Compared to other focal adhesion (FA) proteins such as paxillin, EVL protein expression is very low in human pulmonary endothelial cells (ECs). S1P (1 μM) challenge stimulates translocation of cytosolic EVL to FAs in ECs, which was attenuated by EVL knockdown (KD) by its selective siRNA. S1P also promoted significant EVL translocation to lamellipodia, further confirmed by tracking translocation of EVL-GFP fusion protein upon S1P stimulation in a time-dependent manner. In addition, S1P-mediated cortical actin filament formation is attenuated by EVL KD, further confirming the function of EVL in S1P-induced lamellipodia formation/cortical actin polymerization. S1P stimulates EVL phosphorylation by tyrosine kinase c-Abl which is attenuated by the c-Abl inhibitor, imatinib. Finally, EVL KD attenuated S1P-mediated EC barrier enhancement and paracellular gap resealing reflected by reduced transendothelial electrical resistance (TER) measurements. These findings confirm a novel role for EVL in human lung vascular barrier enhancement and cytoskeleton rearrangement by S1P.

scholarly journals Cytoskeletal proteins in the cell nucleus: a special nuclear actin perspective

2019 ◽  
Vol 30 (15) ◽  
pp. 1781-1785 ◽  
Author(s):  
Piergiorgio Percipalle ◽  
Maria Vartiainen
Keyword(s):  
Gene Expression ◽  
Cell Nucleus ◽  
Cell Biology ◽  
Genome Stability ◽  
Actin Polymerization ◽  
Nuclear Architecture ◽  
Nuclear Lamina ◽  
Cytoskeletal Proteins ◽  
Actin Binding ◽  
Special Focus

The emerging role of cytoskeletal proteins in the cell nucleus has become a new frontier in cell biology. Actin and actin-binding proteins regulate chromatin and gene expression, but importantly they are beginning to be essential players in genome organization. These actin-based functions contribute to genome stability and integrity while affecting DNA replication and global transcription patterns. This is likely to occur through interactions of actin with nuclear components including nuclear lamina and subnuclear organelles. An exciting future challenge is to understand how these actin-based genome-wide mechanisms may regulate development and differentiation by interfering with the mechanical properties of the cell nucleus and how regulated actin polymerization plays a role in maintaining nuclear architecture. With a special focus on actin, here we summarize how cytoskeletal proteins operate in the nucleus and how they may be important to consolidate nuclear architecture for sustained gene expression or silencing.

Lymphocyte-Specific Protein 1 Expression in Eukaryotic Cells Reproduces the Morphologic and Motile Abnormality of NAD 47/89 Neutrophils

Blood ◽  
1998 ◽  
Vol 91 (12) ◽  
pp. 4786-4795 ◽  
Author(s):  
Thomas H. Howard ◽  
John Hartwig ◽  
Casey Cunningham
Keyword(s):  
Actin Polymerization ◽  
Cell Function ◽  
Specific Protein ◽  
Polymorphonuclear Neutrophils ◽  
Actin Binding ◽  
Actin Network ◽  
Cell Surfaces ◽  
Actin Bundles ◽  
Mixed Polarity ◽  
Low Levels

Abstract Despite its name, the actin-binding protein lymphocyte-specific protein1 (LSP1) is found in all hematopoetic cells, and yet its role in cell function remains unclear. Recently, LSP1 was identified as the 47-kD protein overexpressed in the polymorphonuclear neutrophils of patients with a rare neutrophil disorder, neutrophil actin dysfunction with abnormalities of 47-kD and 89-kD proteins (NAD 47/89). These neutrophils are immotile, defective in actin polymerization in response to agonists, and display distinctive, fine, “hairlike” F-actin-rich projections on their cell surfaces. We now show that overexpression of LSP1 produces F-actin bundles that are likely responsible for the morphologic and motile abnormalities characteristic of the NAD 47/89 phenotype. Coincident with LSP1 overexpression, cells from each of several different eukaryotic lines, including a highly motile human melanoma line, develop hairlike surface projections that branch distinctively and contain F-actin and LSP1. The hairlike projections are supported at their core by thick actin bundles, composed of actin filaments of mixed polarity, which periodically anastomose to generate a branching structure. The motility of the melanoma cells is inhibited even at low levels of LSP1 expression. Therefore, these studies show that overexpression of LSP1 alone can recreate the morphologic and motile defects seen in NAD 47/89 and suggest that LSP1 is distinct from other known actin binding proteins in its effect on F-actin network structure.

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