Interplay between the Actin Cytoskeleton, Focal Adhesions and Microtubules

Cell Motility ◽  
2004 ◽  
pp. 75-99 ◽  
Author(s):  
Christoph Ballestrem ◽  
Natalia Magid ◽  
Julia Zonis ◽  
Michael Shtutman ◽  
Alexander Bershadsky
Keyword(s):  
Actin Cytoskeleton ◽  
Focal Adhesions

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.

scholarly journals Piezo2 channel regulates RhoA and actin cytoskeleton to promote cell mechanobiological responses

2018 ◽  
Vol 115 (8) ◽  
pp. 1925-1930 ◽  
Author(s):  
Carlos Pardo-Pastor ◽  
Fanny Rubio-Moscardo ◽  
Marina Vogel-González ◽  
Selma A. Serra ◽  
Alexandros Afthinos ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Actin Polymerization ◽  
Nuclear Translocation ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Force Transmission ◽  
Cellular Processes ◽  
Fyn Kinase ◽  
Downstream Effector ◽  
Metastatic Cells

Actin polymerization and assembly into stress fibers (SFs) is central to many cellular processes. However, how SFs form in response to the mechanical interaction of cells with their environment is not fully understood. Here we have identified Piezo2 mechanosensitive cationic channel as a transducer of environmental physical cues into mechanobiological responses. Piezo2 is needed by brain metastatic cells from breast cancer (MDA-MB-231-BrM2) to probe their physical environment as they anchor and pull on their surroundings or when confronted with confined migration through narrow pores. Piezo2-mediated Ca2+ influx activates RhoA to control the formation and orientation of SFs and focal adhesions (FAs). A possible mechanism for the Piezo2-mediated activation of RhoA involves the recruitment of the Fyn kinase to the cell leading edge as well as calpain activation. Knockdown of Piezo2 in BrM2 cells alters SFs, FAs, and nuclear translocation of YAP; a phenotype rescued by overexpression of dominant-positive RhoA or its downstream effector, mDia1. Consequently, hallmarks of cancer invasion and metastasis related to RhoA, actin cytoskeleton, and/or force transmission, such as migration, extracellular matrix degradation, and Serpin B2 secretion, were reduced in cells lacking Piezo2.

Force-dependent vinculin binding to talin in live cells: a crucial step in anchoring the actin cytoskeleton to focal adhesions

2014 ◽  
Vol 306 (6) ◽  
pp. C607-C620 ◽  
Author(s):  
Hiroaki Hirata ◽  
Hitoshi Tatsumi ◽  
Chwee Teck Lim ◽  
Masahiro Sokabe
Keyword(s):  
Actin Cytoskeleton ◽  
Focal Adhesions ◽  
Living Cells ◽  
Live Cells ◽  
Mechanical Forces ◽  
Actin Network ◽  
Crucial Step

Mechanical forces play a pivotal role in the regulation of focal adhesions (FAs) where the actin cytoskeleton is anchored to the extracellular matrix through integrin and a variety of linker proteins including talin and vinculin. The localization of vinculin at FAs depends on mechanical forces. While in vitro studies have demonstrated the force-induced increase in vinculin binding to talin, it remains unclear whether such a mechanism exists at FAs in vivo. In this study, using fibroblasts cultured on elastic silicone substrata, we have examined the role of forces in modulating talin-vinculin binding at FAs. Stretching the substrata caused vinculin accumulation at talin-containing FAs, and this accumulation was abrogated by expressing the talin-binding domain of vinculin (domain D1, which inhibits endogenous vinculin from binding to talin). These results indicate that mechanical forces loaded to FAs facilitate vinculin binding to talin at FAs. In cell-protruding regions, the actin network moved backward over talin-containing FAs in domain D1-expressing cells while it was anchored to FAs in control cells, suggesting that the force-dependent vinculin binding to talin is crucial for anchoring the actin cytoskeleton to FAs in living cells.

Cell fusion mediates dramatic alterations in the actin cytoskeleton, focal adhesions, and E-cadherin in trophoblastic cells

Cytoskeleton ◽  
2014 ◽  
Vol 71 (4) ◽  
pp. 241-256 ◽  
Author(s):  
Atsuko Ishikawa ◽  
Waka Omata ◽  
William E. Ackerman ◽  
Toshiyuki Takeshita ◽  
Dale D. Vandré ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Cell Fusion ◽  
Focal Adhesions ◽  
Trophoblastic Cells ◽  
E Cadherin

Regulation of actin organisation by TGF-beta in H-ras-transformed fibroblasts

1999 ◽  
Vol 112 (8) ◽  
pp. 1169-1179 ◽  
Author(s):  
A. Moustakas ◽  
C. Stournaras
Keyword(s):  
Growth Factor ◽  
Actin Cytoskeleton ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Focal Adhesions ◽  
Small Gtpase ◽  
Morphological Alteration ◽  
Direct Role ◽  
Transformed Fibroblasts ◽  
Growth Factor Beta

The actin cytoskeleton undergoes architectural changes during the processes of cell transformation and tumourigenesis. Transforming growth factors beta arrest cell cycle progression, regulate differentiation and modulate the onset of oncogenesis and tumourigenesis. Here, we investigated the direct role of transforming growth factor beta-1 in altering the transformed phenotype and regulating the actin organisation of oncogenic fibroblasts that constitutively or inducibly express the H-ras oncogene. Following transforming growth factor beta-1 treatment, these transformed fibroblasts undergo a dramatic morphological alteration that includes a discrete reorganisation of their actin cytoskeleton and focal adhesions. Quantitative biochemical analysis demonstrated that transforming growth factor beta-1 potently induced polymerisation of globular to filamentous actin, thus corroborating the morphological analysis. The effect of transforming growth factor beta-1 on the cytoskeleton correlates with the ability of this cytokine to suppress anchorage-independent growth of the transformed fibroblasts. Furthermore, transforming growth factor beta-1 upregulates considerably the levels of the RhoB small GTPase and less the RhoA levels. Finally, The beta GTPase inhibitor, C3 exotransferase, blocks the ability of TGF-beta1 to induce cytoskeletal reorganisation. These findings indicate that transforming growth factor beta can regulate cell morphology and growth in a concerted manner possibly via mechanisms that control the actin cytoskeleton.

Migration Potential of Human Mesenchymal Stromal Cells Is Determined by Origin of Tissue Rather Than Their Developmental Stage

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4743-4743
Author(s):  
Marijke W. Maijenburg ◽  
Willy A. Noort ◽  
Marion Kleijer ◽  
Charlotte J.A. Kompier ◽  
Kees Weijer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Synergistic Effect ◽  
Actin Cytoskeleton ◽  
Developmental Stage ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ex Vivo ◽  
Focal Adhesions ◽  
Migration Potential ◽  
Migration Capacity

Abstract It is thought that adult mesenchymal stromal cells (MSC) are important for tissue repair and maintenance. Crucial in these processes is the presence of MSC at the site of injury, however the recruitment and migration of MSC towards their destiny is poorly understood. With respect to future cell therapy, we are studying the process of migration of various human mesenchymal stem cell sources, and hypothesize that only a subpopulation of ex vivo expanded mesenchymal stem cells is capable of specific homing. For this purpose, MSC from different sources i.e. fetal lung (FL), fetal bone marrow (FBM), adult bone marrow (ABM) and adult adipose tissue (AT) were derived by plastic adherence and subsequently expanded. All MSC sources were characterized as CD73+, CD90+, CD105+, CD34− and CD45−. MSC (P4-9) were allowed to migrate for 4h towards SDF-1a, PDGF-BB, HGF, bFGF or FCS over fibronectin-coated 12 mm pore size transwell plates. FL-MSC migrated significantly better towards SDF-1a as compared to ABM-MSC or AT-MSC. This enhanced migration capacity towards SDF-1a is specific for FL-MSC since AT-MSC migrated better towards FCS as compared to FL-MSC. Even ABM-MSC responded better to FCS than FL-MSC. This suggests that MSC originating from all sources are able to migrate but require different triggers to induce migration. In order to elucidate whether the observed differences in migration potential were due to developmental stage, cultured MSC derived from fetal bone marrow were tested as well. No significant differences in migration capacity were observed between adult and fetal BM- MSC for any of the (chemotactic) stimuli evaluated. Interestingly, FL-MSC had a significant increased migration capacity as compared to FBM-MSC towards SDF-1a, PDGF-BB and HGF, suggesting that the origin of tissue may determine migration capacity of ex vivo expanded MSC. Since it was observed that only a small percentage of the cultured MSC were able to migrate towards the various stimuli, checkerboard migration was performed to elucidate whether a synergistic effect could be observed. No synergistic effect was observed between SDF and PDGF, SDF and FCS or PDGF and FCS in FL-MSC, suggesting that there may be one subpopulation of MSC that possesses migratory capacities. When studying the SDF-1-induced migratory subpopulation in more detail, it was observed that, after migration, migratory MSC originating from all tissue sources maintain their proliferation and differentiation capacity and express CXCR4 at a higher level than MSC that did not migrate. To be able to migrate, cells have to rearrange their actin cytoskeleton and focal adhesions. These processes can be initiated by various chemokines and growth factors. In response to SDF or FCS, morphological changes were observed in ABM-MSC by confocal microscopy. Cells became smaller and membrane protrusions appeared, whereas this was absent in the control. Furthermore, upon stimulation with SDF, PDGF and FCS, tyrosine-phosphorylation of the adapter protein paxillin that links the actin cytoskeleton to focal adhesions was increased. In conclusion, our results suggest that migration potential of ex vivo expanded MSC derived from various adult and fetal tissues have different migratory capacity towards growth factor and chemokine stimuli and may involve paxillin phosphorylation. Our data indicate that further studies on the migratory subpopulation(s) within the heterogeneous population of culture expanded MSC will contribute to unravel how and which MSC will be of interest for future cellular therapies.

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