scholarly journals T-Plastin reinforces membrane protrusions to bridge matrix gaps during cell migration

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Damien Garbett ◽  
Anjali Bisaria ◽  
Changsong Yang ◽  
Dannielle G. McCarthy ◽  
Arnold Hayer ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Actin Filaments ◽  
Myosin Ii ◽  
Adhesion Sites ◽  
Membrane Protrusions ◽  
And Migration ◽  
Muscle Myosin ◽  
Migrating Cells

Abstract Migrating cells move across diverse assemblies of extracellular matrix (ECM) that can be separated by micron-scale gaps. For membranes to protrude and reattach across a gap, actin filaments, which are relatively weak as single filaments, must polymerize outward from adhesion sites to push membranes towards distant sites of new adhesion. Here, using micropatterned ECMs, we identify T-Plastin, one of the most ancient actin bundling proteins, as an actin stabilizer that promotes membrane protrusions and enables bridging of ECM gaps. We show that T-Plastin widens and lengthens protrusions and is specifically enriched in active protrusions where F-actin is devoid of non-muscle myosin II activity. Together, our study uncovers critical roles of the actin bundler T-Plastin to promote protrusions and migration when adhesion is spatially-gapped.

scholarly journals Scribble, Lgl1, and myosin II form a complex in vivo to promote directed cell migration

2020 ◽  
Vol 31 (20) ◽  
pp. 2234-2248
Author(s):  
Maha Abedrabbo ◽  
Shoshana Ravid
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Myosin Ii ◽  
Leading Edge ◽  
Directed Cell Migration ◽  
Lethal Giant Larvae ◽  
And Migration ◽  
Migrating Cells

Here we show that Scribble (Scrib), Lethal giant larvae 1 (Lgl1), and myosin II form a complex in vivo and colocalize at the cell leading edge of migrating cells, and this colocalization is interdependent. Scrib and Lgl1 are required for proper cell adhesion, polarity, and migration.

scholarly journals Microinjection of antibodies against talin inhibits the spreading and migration of fibroblasts

1992 ◽  
Vol 102 (4) ◽  
pp. 753-762
Author(s):  
G.H. Nuckolls ◽  
L.H. Romer ◽  
K. Burridge
Keyword(s):  
Extracellular Matrix ◽  
Tissue Culture ◽  
Actin Filaments ◽  
Focal Adhesions ◽  
Cell Spreading ◽  
And Migration ◽  
Extracellular Matrix Receptors

Talin is believed to be one of the key proteins involved in linking actin filaments to extracellular matrix receptors in focal adhesions. Our strategy for studying the function of talin has been to inactivate talin in living fibroblasts in tissue culture through the microinjection of affinity-purified, polyclonal anti-talin antibodies. The effect of the injected anti-talin antibodies on cell spreading was found to depend on how recently the cells had been plated. Cells that were in the process of spreading on a fibronectin substratum, and which had newly developed focal adhesions, were induced to round up and to disassemble many of the adhesions. However, if fibroblasts were allowed to spread completely before they were microinjected with the anti-talin antibody, focal adhesions remained intact and the flat morphology of the cells was unaffected. The percentage of cells that were able to maintain a spread morphology despite the injection of anti-talin antibodies increased during the first few hours after plating on fibronectin substrata. Fibroblasts that were allowed to spread completely before microinjection with the anti-talin antibody retained both intact focal adhesions and a flat, well-spread morphology, but failed to migrate effectively. Our experiments do not directly address the role of talin in mature focal adhesions, but they indicate that talin is essential for the spreading and migration of fibroblasts on fibronectin as well as for the development and initial maintenance of focal adhesions on this substratum.

scholarly journals Stiffer Matrix Accelerates Migration of Hepatocellular Carcinoma Cells through Enhanced Aerobic Glycolysis Via the MAPK-YAP Signaling

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 490 ◽  
Author(s):  
Qiu-Ping Liu ◽  
Qing Luo ◽  
Bin Deng ◽  
Yang Ju ◽  
Guan-Bin Song
Keyword(s):  
Hepatocellular Carcinoma ◽  
Extracellular Matrix ◽  
Cell Migration ◽  
Aerobic Glycolysis ◽  
Mapk Signaling ◽  
Carcinoma Cells ◽  
Metabolic Reprogramming ◽  
Signaling Cascade ◽  
And Migration ◽  
Hcc Cells

Increased extracellular matrix (ECM) stiffness and metabolic reprogramming of cancer cells are two fundamental mediators of tumor progression, including hepatocellular carcinoma (HCC). Yet, the correlation between ECM stiffness and excessive aerobic glycolysis in promoting the development of HCC remains unknown. Here, we demonstrated that stiffer ECM promotes HCC cell migration depending on their accelerated aerobic glycolysis. Our results also indicated that stiffer ECM-induced YAP activation plays a major role in promoting aerobic glycolysis of HCC cells. Moreover, we showed that JNK and p38 MAPK signaling are critical for mediating YAP activation in HCC cells. Together, our findings established that the MAPK-YAP signaling cascade that act as a mechanotransduction pathway is essential for promoting HCC cell aerobic glycolysis and migration in response to ECM stiffness.

scholarly journals Testing the limits of cell migration

2013 ◽  
Vol 201 (7) ◽  
pp. 965-965 ◽  
Author(s):  
Ben Short
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Migrating Cells

Migrating cells are restricted by their ability to squeeze their nuclei through pores in the extracellular matrix.

scholarly journals One-dimensional topography underlies three-dimensional fibrillar cell migration

2009 ◽  
Vol 184 (4) ◽  
pp. 481-490 ◽  
Author(s):  
Andrew D. Doyle ◽  
Francis W. Wang ◽  
Kazue Matsumoto ◽  
Kenneth M. Yamada
Keyword(s):  
Cell Culture ◽  
Extracellular Matrix ◽  
Cell Migration ◽  
Myosin Ii ◽  
Three Dimensional ◽  
Two Dimensional ◽  
Ligand Density ◽  
One Dimensional ◽  
3D Cell Migration ◽  
Striking Contrast

Current concepts of cell migration were established in regular two-dimensional (2D) cell culture, but the roles of topography are poorly understood for cells migrating in an oriented 3D fibrillar extracellular matrix (ECM). We use a novel micropatterning technique termed microphotopatterning (μPP) to identify functions for 1D fibrillar patterns in 3D cell migration. In striking contrast to 2D, cell migration in both 1D and 3D is rapid, uniaxial, independent of ECM ligand density, and dependent on myosin II contractility and microtubules (MTs). 1D and 3D migration are also characterized by an anterior MT bundle with a posterior centrosome. We propose that cells migrate rapidly through 3D fibrillar matrices by a 1D migratory mechanism not mimicked by 2D matrices.

scholarly journals So far, yet so close: α-Catenin dimers help migrating cells get together

2017 ◽  
Vol 216 (11) ◽  
pp. 3437-3439
Author(s):  
Laura Machesky ◽  
Vania M.M. Braga
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Active Plasma ◽  
Cell Biol ◽  
Membrane Protrusions ◽  
Freely Moving ◽  
And Migration ◽  
Migrating Cells

Epithelial cells in tissues use their actin cytoskeletons to stick together, whereas unattached cells make active plasma membrane protrusions to migrate. In this issue, Wood et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201612006) show that the junction component α-catenin is critical in freely moving cells to promote adhesion and migration.

scholarly journals Membrane-proximal F-actin restricts local membrane protrusions and directs cell migration

Science ◽  
2020 ◽  
Vol 368 (6496) ◽  
pp. 1205-1210 ◽  
Author(s):  
Anjali Bisaria ◽  
Arnold Hayer ◽  
Damien Garbett ◽  
Daniel Cohen ◽  
Tobias Meyer
Keyword(s):  
Plasma Membrane ◽  
Cell Migration ◽  
Cell Polarization ◽  
Density Gradients ◽  
Membrane Protrusion ◽  
Fluorescent Reporter ◽  
Membrane Protrusions ◽  
Directed Polymerization ◽  
Actin Concentration ◽  
Migrating Cells

Cell migration is driven by local membrane protrusion through directed polymerization of F-actin at the front. However, F-actin next to the plasma membrane also tethers the membrane and thus resists outgoing protrusions. Here, we developed a fluorescent reporter to monitor changes in the density of membrane-proximal F-actin (MPA) during membrane protrusion and cell migration. Unlike the total F-actin concentration, which was high in the front of migrating cells, MPA density was low in the front and high in the back. Back-to-front MPA density gradients were controlled by higher cofilin-mediated turnover of F-actin in the front. Furthermore, nascent membrane protrusions selectively extended outward from areas where MPA density was reduced. Thus, locally low MPA density directs local membrane protrusions and stabilizes cell polarization during cell migration.

scholarly journals Periodic Mechanical Stress Induces Extracellular Matrix Expression and Migration of Rat Nucleus Pulposus Cells Through Src-GIT1-ERK1/2 Signaling Pathway

2018 ◽  
Vol 50 (4) ◽  
pp. 1510-1521 ◽  
Author(s):  
Gongming Gao ◽  
Haibo Li ◽  
Yongjing Huang ◽  
Jianjian Yin ◽  
Yuqing Jiang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Mechanical Stress ◽  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
Signal Transduction Pathway ◽  
Direct Interaction ◽  
Nucleus Pulposus Cells ◽  
Immunoprecipitation Assay ◽  
And Migration

Background/Aims: Periodic mechanical stress has been shown to promote extracellular matrix (ECM) synthesis and cell migration of nucleus pulposus (NP) cells, however, the mechanisms need to be fully elucidated. The present study aimed to investigate the signal transduction pathway in the regulation of NP cells under periodic mechanical stress. Methods: Primary rat NP cells were isolated and seeded on glass slides, and then treated in our self-developed periodic stress field culture system. To further explore the mechanisms, data were analyzed by scratch-healing assay, quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis, western blotting, and co-immunoprecipitation assay. Results: Under periodic mechanical stress, the mRNA expression of ECM collagen 2A1 (Col2A1) and aggrecan, and migration of NP cells were significantly increased (P < 0.05 for each), associating with increases in the phosphorylation of Src, GIT1, and ERK1/2 (P < 0.05 for each). Pretreatment with the Src inhibitor PP2 reduced periodic mechanical stress-induced ECM synthesis and cell migration of NP cells (P < 0.05 for each), while the phosphorylation of GIT1 and ERK1/2 were inhibited. ECM synthesis, cell migration, and phosphorylation of ERK1/2 were inhibited after pretreatment with the small interfering RNA for GIT1 in NP cells under periodic mechanical stress (P < 0.05 for each), whereas the phosphorylation of Src was not affected. Pretreatment with the ERK1/2 inhibitor PD98059 reduced periodic mechanical stress-induced ECM synthesis and cell migration of NP cells (P < 0.05 for each). Co-immunoprecipitation assay showed that there was a direct interaction between Src and GIT1 and between GIT1 and ERK1/2. Conclusion: In conclusion, periodic mechanical stress induced ECM expression and migration of NP cells via Src-GIT1-ERK1/2 signaling pathway, playing an important role in regulation of NP cells.

scholarly journals Local extracellular matrix alignment directs cellular protrusion dynamics and migration through Rac1 and FAK

2016 ◽  
Vol 8 (8) ◽  
pp. 821-835 ◽  
Author(s):  
Shawn P. Carey ◽  
Zachary E. Goldblatt ◽  
Karen E. Martin ◽  
Bethsabe Romero ◽  
Rebecca M. Williams ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Collagen Matrices ◽  
Fiber Alignment ◽  
Direct Cell ◽  
And Migration ◽  
Cellular Protrusion

Fiber alignment within tumor-mimetic engineered collagen matrices drives FAK- and Rac1-dependent cellular anisotropy that promotes protrusions along fibers and suppresses off-axis protrusions to direct cell migration.

scholarly journals Tiam1 interaction with the PAR complex promotes talin-mediated Rac1 activation during polarized cell migration

2012 ◽  
Vol 199 (2) ◽  
pp. 331-345 ◽  
Author(s):  
Shujie Wang ◽  
Takashi Watanabe ◽  
Kenji Matsuzawa ◽  
Akira Katsumi ◽  
Mai Kakeno ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Cell Migration ◽  
Protein Kinase ◽  
Leading Edge ◽  
Cell Spreading ◽  
Kinase C ◽  
Rac1 Activity ◽  
Directional Movement ◽  
And Migration ◽  
Migrating Cells

Migrating cells acquire front-rear polarity with a leading edge and a trailing tail for directional movement. The Rac exchange factor Tiam1 participates in polarized cell migration with the PAR complex of PAR3, PAR6, and atypical protein kinase C. However, it remains largely unknown how Tiam1 is regulated and contributes to the establishment of polarity in migrating cells. We show here that Tiam1 interacts directly with talin, which binds and activates integrins to mediate their signaling. Tiam1 accumulated at adhesions in a manner dependent on talin and the PAR complex. The interactions of talin with Tiam1 and the PAR complex were required for adhesion-induced Rac1 activation, cell spreading, and migration toward integrin substrates. Furthermore, Tiam1 acted with talin to regulate adhesion turnover. Thus, we propose that Tiam1, with the PAR complex, binds to integrins through talin and, together with the PAR complex, thereby regulates Rac1 activity and adhesion turnover for polarized migration.

Sign in / Sign up

Export Citation Format

Share Document