scholarly journals Actin Dynamics Associated with Focal Adhesions

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Corina Ciobanasu ◽  
Bruno Faivre ◽  
Christophe Le Clainche
Keyword(s):  
Extracellular Matrix ◽  
Molecular Mechanisms ◽  
Body Force ◽  
Focal Adhesions ◽  
Stress Fibers ◽  
Actin Dynamics ◽  
Actin Assembly ◽  
Force Transmission ◽  
Cell Matrix ◽  
Cell Matrix Adhesion

Cell-matrix adhesion plays a major role during cell migration. Proteins from adhesion structures connect the extracellular matrix to the actin cytoskeleton, allowing the growing actin network to push the plasma membrane and the contractile cables (stress fibers) to pull the cell body. Force transmission to the extracellular matrix depends on several parameters including the regulation of actin dynamics in adhesion structures, the contractility of stress fibers, and the mechanosensitive response of adhesion structures. Here we highlight recent findings on the molecular mechanisms by which actin assembly is regulated in adhesion structures and the molecular basis of the mechanosensitivity of focal adhesions.

Hierarchical assembly of cell–matrix adhesion complexes

2004 ◽  
Vol 32 (3) ◽  
pp. 416-420 ◽  
Author(s):  
R. Zaidel-Bar ◽  
M. Cohen ◽  
L. Addadi ◽  
B. Geiger
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Cellular Migration ◽  
Hierarchical Assembly ◽  
Surface Recognition ◽  
Cell Matrix ◽  
Molecular Events ◽  
Cell Matrix Adhesion

The adhesion of cells to the extracellular matrix is a dynamic process, mediated by a series of cell-surface and matrix-associated molecules that interact with each other in a spatially and temporally regulated manner. These interactions play a major role in tissue formation, cellular migration and the induction of adhesion-mediated transmembrane signals. In this paper, we show that the formation of matrix adhesions is a hierarchical process, consisting of several sequential molecular events. One of the earliest steps in surface recognition is mediated, in some cells, by a 1 μm-thick cell-surface hyaluronan coat, which precedes the establishment of stable, cytoskeleton-associated adhesions. The earliest forms of these integrin-mediated contacts are dot-shaped FXs (focal complexes), which are formed under the protrusive lamellipodium of migrating cells. These adhesions recruit, sequentially, different anchor proteins that are involved in binding the actin cytoskeleton to the membrane. Conspicuous in its absence from FXs is zyxin, which is recruited to these sites only on retraction of the leading edge and the transformation of the FXs into a focal adhesion. Continuing application of force to focal adhesions results in the formation of fibrillar adhesions and reorganization of the extracellular matrix. The formation of these adhesions depends on actomyosin contractility and matrix pliability.

scholarly journals WT1-interacting protein (Wtip) regulates podocyte phenotype by cell-cell and cell-matrix contact reorganization

2012 ◽  
Vol 302 (1) ◽  
pp. F103-F115 ◽  
Author(s):  
Jane H. Kim ◽  
Amitava Mukherjee ◽  
Sethu M. Madhavan ◽  
Martha Konieczkowski ◽  
John R. Sedor
Keyword(s):  
Kinase Inhibitor ◽  
Adherens Junctions ◽  
Focal Adhesions ◽  
Stress Fibers ◽  
Actin Dynamics ◽  
Transcriptional Responses ◽  
Interacting Protein ◽  
Cell Matrix ◽  
Actin Stress Fibers ◽  
Cell Cell

Podocytes respond to environmental cues by remodeling their slit diaphragms and cell-matrix adhesive junctions. Wt1-interacting protein (Wtip), an Ajuba family LIM domain scaffold protein expressed in the podocyte, coordinates cell adhesion changes and transcriptional responses to regulate podocyte phenotypic plasticity. We evaluated effects of Wtip on podocyte cell-cell and cell-matrix contact organization using gain-of- and loss-of-function methods. Endogenous Wtip targeted to focal adhesions in adherent but isolated podocytes and then shifted to adherens junctions after cells made stable, homotypic contacts. Podocytes with Wtip knockdown (shWtip) adhered but failed to spread normally. Noncontacted shWtip podocytes did not assemble actin stress fibers, and their focal adhesions failed to mature. As shWtip podocytes established cell-cell contacts, stable adherens junctions failed to form and F-actin structures were disordered. In shWtip cells, cadherin and β-catenin clustered in irregularly distributed spots that failed to laterally expand. Cell surface biotinylation showed diminished plasma membrane cadherin, β-catenin, and α-catenin in shWtip podocytes, although protein expression was similar in shWtip and control cells. Since normal actin dynamics are required for organization of adherens junctions and focal adhesions, we determined whether Wtip regulates F-actin assembly. Undifferentiated podocytes did not elaborate F-actin stress fibers, but when induced to overexpress WTIP, formed abundant stress fibers, a process blocked by the RhoA inhibitor C3 toxin and a RhoA kinase inhibitor. WTIP directly interacted with Rho guanine nucleotide exchange factor (GEF) 12 (Arhgef12), a RhoA-specific GEF enriched in the glomerulus. In conclusion, stable assembly of podocyte adherens junctions and cell-matrix contacts requires Wtip, a process that may be mediated by spatiotemporal regulation of RhoA activity through appropriate targeting of Arhgef12.

scholarly journals Review of PIP2 in Cellular Signaling, Functions and Diseases

2020 ◽  
Vol 21 (21) ◽  
pp. 8342
Author(s):  
Kalpana Mandal
Keyword(s):  
Molecular Mechanisms ◽  
Membrane Dynamics ◽  
Actin Dynamics ◽  
Cellular Functions ◽  
Phosphatidylinositol Bisphosphate ◽  
Cell Matrix ◽  
Intracellular Proteins ◽  
Specific Proteins ◽  
Cellular Compartments ◽  
Cell Matrix Adhesion

Phosphoinositides play a crucial role in regulating many cellular functions, such as actin dynamics, signaling, intracellular trafficking, membrane dynamics, and cell–matrix adhesion. Central to this process is phosphatidylinositol bisphosphate (PIP2). The levels of PIP2 in the membrane are rapidly altered by the activity of phosphoinositide-directed kinases and phosphatases, and it binds to dozens of different intracellular proteins. Despite the vast literature dedicated to understanding the regulation of PIP2 in cells over past 30 years, much remains to be learned about its cellular functions. In this review, we focus on past and recent exciting results on different molecular mechanisms that regulate cellular functions by binding of specific proteins to PIP2 or by stabilizing phosphoinositide pools in different cellular compartments. Moreover, this review summarizes recent findings that implicate dysregulation of PIP2 in many diseases

scholarly journals Rab40/Cullin5 complex regulates EPLIN and actin cytoskeleton dynamics during cell migration and invasion

2021 ◽  
Author(s):  
Erik S Linklater ◽  
Emily Duncan ◽  
Ke Jun Han ◽  
Algirdas Kaupinis ◽  
Mindaugas Valius ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Focal Adhesion ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Stress Fibers ◽  
Actin Dynamics ◽  
Migration And Invasion ◽  
Matrix Remodeling ◽  
Cell Migration And Invasion

Rab40b is a SOCS box containing protein that regulates the secretion of MMPs to facilitate extracellular matrix remodeling during cell migration. Here we show that Rab40b interacts with Cullin5 via the Rab40b SOCS domain. We demonstrate that loss of Rab40b/Cullin5 binding decreases cell motility and invasive potential, and show that defective cell migration and invasion stem from alteration to the actin cytoskeleton, leading to decreased invadopodia formation, decreased actin dynamics at the leading edge, and an increase in stress fibers. We also show that these stress fibers anchor at less dynamic, more stable focal adhesions. Mechanistically, changes in the cytoskeleton and focal adhesion dynamics are mediated in part by EPLIN, which we demonstrate to be a binding partner of Rab40b and a target for Rab40b/Cullin5 dependent localized ubiquitylation and degradation. Thus, we propose a model where the Rab40b/Cullin5 dependent ubiquitylation regulates EPLIN localization to promote cell migration and invasion by altering focal adhesion and cytoskeletal dynamics.

Ezrin regulates cell-cell and cell-matrix adhesion, a possible role with E-cadherin/beta-catenin

1999 ◽  
Vol 112 (18) ◽  
pp. 3081-3090 ◽  
Author(s):  
S. Hiscox ◽  
W.G. Jiang
Keyword(s):  
Cancer Cells ◽  
Focal Adhesions ◽  
Beta Catenin ◽  
Matrix Adhesion ◽  
Cell Matrix ◽  
Ezrin Expression ◽  
Coated Surfaces ◽  
Cell Matrix Adhesion ◽  
E Cadherin ◽  
Cell Cell

Ezrin, radixin, moesin and merlin form a subfamily of conserved proteins in the band 4.1 superfamily. The function of these proteins is to link the plasma membrane to the actin cytoskeleton. Merlin is defective or absent in schwannomas and meningiomas and has been suggested to function as a tumour suppressor. In this study, we have examined the role of ezrin as a potential regulator of the adhesive and invasive behaviour of tumour cells. We have shown that following inhibition of ezrin expression in colo-rectal cancer cells using antisense oligonucleotides, these cells displayed a reduced cell-cell adhesiveness together with a gain in their motile and invasive behaviour. These cells also displayed increased spreading over matrix-coated surfaces. Immunofluorescence studies revealed that antisense-treated cells also displayed an increased staining of paxillin in areas representing focal adhesions. Furthermore, coprecipitation studies revealed an association of ezrin with E-cadherin and beta-catenin. Induction of the phosphorylation of ezrin by orthovanadate and hepatocyte growth factor/scatter factor resulted in changes similar to those seen with antisense treatment, together with a marked decrease in the association of ezrin with both beta-catenin and E-cadherin. It is concluded that ezrin regulates cell-cell and cell-matrix adhesion, by interacting with cell adhesion molecules E-cadherin and beta-catenin, and may thus play an important role in the control of adhesion and invasiveness of cancer cells.

scholarly journals Serotonin 2A (5-HT2A) receptor affects cell–matrix adhesion and the formation and maintenance of stress fibers in HEK293 cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Joe Anand Kumar John Jayakumar ◽  
Mitradas. M. Panicker ◽  
Basudha Basu
Keyword(s):  
Nervous System ◽  
Neural Circuits ◽  
Stress Fibers ◽  
Hek293 Cells ◽  
Matrix Adhesion ◽  
Cell Matrix ◽  
Cell Matrix Adhesion ◽  
G Protein Coupled ◽  
Serotonin 2A ◽  
Stimulation Of

Abstract5-HT2A, a G-protein coupled receptor, is widely expressed in the human body, including in the gastrointestinal tract, platelets and the nervous system. It mediates various functions, for e.g. learning, memory, mood regulation, platelet aggregation and vasoconstriction, but its involvement in cell-adhesion remains largely unknown. Here we report a novel role for 5-HT2A in cell–matrix adhesion.In HEK293 cells, which are loosely adherent, expression and stimulation of human or rat 5-HT2A receptor by agonists such as serotonin or 2,5-dimethoxy-4-iodoamphetamine (DOI) led to a significant increase in adhesion, while inhibition of 5-HT2A by antipsychotics, such as risperidone, olanzapine or chlorpromazine prevented it. 5-HT2A activation gave rise to stress fibers in these cells and was also required for their maintenance. Mechanistically, the 5-HT2A-mediated adhesion was mediated by downstream PKC and Rho signaling. Since 5-HT2A is associated with many disorders such as dementia, depression and schizophrenia, its role in cell–matrix adhesion could have implications for neural circuits.

scholarly journals Zasp is required for the assembly of functional integrin adhesion sites

2007 ◽  
Vol 179 (7) ◽  
pp. 1583-1597 ◽  
Author(s):  
Klodiana Jani ◽  
Frieder Schöck
Keyword(s):  
Focal Adhesions ◽  
Myotendinous Junction ◽  
Lim Domain ◽  
Transmembrane Receptors ◽  
Cell Matrix ◽  
Adhesion Sites ◽  
Alternatively Spliced ◽  
Dependent Cell ◽  
Cell Matrix Adhesion ◽  
Myotendinous Junctions

The integrin family of heterodimeric transmembrane receptors mediates cell–matrix adhesion. Integrins often localize in highly organized structures, such as focal adhesions in tissue culture and myotendinous junctions in muscles. Our RNA interference screen for genes that prevent integrin-dependent cell spreading identifies Z band alternatively spliced PDZ-motif protein (zasp), encoding the only known Drosophila melanogaster Alp/Enigma PDZ-LIM domain protein. Zasp localizes to integrin adhesion sites and its depletion disrupts integrin adhesion sites. In tissues, Zasp colocalizes with βPS integrin in myotendinous junctions and with α-actinin in muscle Z lines. Zasp also physically interacts with α-actinin. Fly larvae lacking Zasp do not form Z lines and fail to recruit α-actinin to the Z line. At the myotendinous junction, muscles detach in zasp mutants with the onset of contractility. Finally, Zasp interacts genetically with integrins, showing that it regulates integrin function. Our observations point to an important function for Zasp in the assembly of integrin adhesion sites both in cell culture and in tissues.

MATHEMATICAL MODELLING OF CANCER INVASION: THE IMPORTANCE OF CELL–CELL ADHESION AND CELL–MATRIX ADHESION

2011 ◽  
Vol 21 (04) ◽  
pp. 719-743 ◽  
Author(s):  
MARK A. J. CHAPLAIN ◽  
MIROSŁAW LACHOWICZ ◽  
ZUZANNA SZYMAŃSKA ◽  
DARIUSZ WRZOSEK
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Cancer Cells ◽  
Classical Solutions ◽  
Invasion Process ◽  
Open Problems ◽  
Matrix Adhesion ◽  
Cell Matrix ◽  
Cell Matrix Adhesion ◽  
Cell Cell

The process of invasion of tissue by cancer cells is crucial for metastasis — the formation of secondary tumours — which is the main cause of mortality in patients with cancer. In the invasion process itself, adhesion, both cell–cell and cell–matrix, plays an extremely important role. In this paper, a mathematical model of cancer cell invasion of the extracellular matrix is developed by incorporating cell–cell adhesion as well as cell–matrix adhesion into the model. Considering the interactions between cancer cells, extracellular matrix and matrix degrading enzymes, the model consists of a system of reaction–diffusion partial integro–differential equations, with nonlocal (integral) terms describing the adhesive interactions between cancer cells and the host tissue, i.e. cell–cell adhesion and cell–matrix adhesion. Having formulated the model, we prove the existence and uniqueness of global in time classical solutions which are uniformly bounded. Then, using computational simulations, we investigate the effects of the relative importance of cell–cell adhesion and cell–matrix adhesion on the invasion process. In particular, we examine the roles of cell–cell adhesion and cell–matrix adhesion in generating heterogeneous spatio-temporal solutions. Finally, in the discussion section, concluding remarks are made and open problems are indicated.

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