The Experts below are selected from a list of 216 Experts worldwide ranked by ideXlab platform
Maura Grealy - One of the best experts on this subject based on the ideXlab platform.
-
Plakoglobin expression and localization in zebrafish embryo development.
Biochemical Society Transactions, 2004Co-Authors: Eva D. Martin, Maura GrealyAbstract:Plakoglobin (γ-catenin) and β-catenin are major components of the adherens junctions and can be localized to the nucleus by activation of the Wnt signalling pathway. In addition, plakoglobin is also found in desmosomes, a vertebrate-specific cell–cell Adhesion Structure. Plakoglobin expression and localization were examined at the protein level during zebrafish embryonic development by Western blotting and confocal microscopy. Plakoglobin was expressed throughout embryo development at the protein level. Western blotting revealed that embryonic plakoglobin protein content increased between 12- and 24-h post-fertilization (hpf). Confocal microscopy showed that at stages up to 12 hpf, plakoglobin and β-catenin were co-localized and expressed in both the nucleus and in cell–cell junctions. At 24- and 72-hpf, separate patterns were seen for plakoglobin and β-catenin. These data indicate that plakoglobin localization in the heart region shifts from adherens junctions to desmosomes during heart chamber development.
-
Plakoglobin expression and localization in zebrafish embryo development.
Biochemical Society transactions, 2004Co-Authors: Eva D. Martin, Maura GrealyAbstract:Plakoglobin (gamma-catenin) and beta-catenin are major components of the adherens junctions and can be localized to the nucleus by activation of the Wnt signalling pathway. In addition, plakoglobin is also found in desmosomes, a vertebrate-specific cell-cell Adhesion Structure. Plakoglobin expression and localization were examined at the protein level during zebrafish embryonic development by Western blotting and confocal microscopy. Plakoglobin was expressed throughout embryo development at the protein level. Western blotting revealed that embryonic plakoglobin protein content increased between 12- and 24-h post-fertilization (hpf). Confocal microscopy showed that at stages up to 12 hpf, plakoglobin and beta-catenin were co-localized and expressed in both the nucleus and in cell-cell junctions. At 24- and 72-hpf, separate patterns were seen for plakoglobin and beta-catenin. These data indicate that plakoglobin localization in the heart region shifts from adherens junctions to desmosomes during heart chamber development.
Vivek B Shenoy - One of the best experts on this subject based on the ideXlab platform.
-
a chemo mechanical model for extracellular matrix and nuclear rigidity regulated size of focal Adhesion plaques
Biophysical Journal, 2016Co-Authors: Xuan Cao, Yuan Lin, Tristian P Driscoll, Janusz Francobarraza, Edna Cukierman, Robert L Mauck, Vivek B ShenoyAbstract:In this work, a chemo-mechanical model describing the growth dynamics of cell-matrix Adhesion Structures (i.e. focal Adhesions (FAs)) is developed. We show that there are three regimes for FA evolution depending on their size. Specifically, nascent Adhesions with initial lengths below a critical value that are yet to engage in actin fibers will dissolve, whereas bigger ones will grow into mature FAs with a steady state size. In Adhesions where growth surpasses the steady state size, disassembly will occur until their sizes are reduced back to the equilibrium state. This finding arises from the fact that polymerization of Adhesion proteins is force-dependent. Under actomyosin contraction, individual integrin bonds within small FAs must transmit higher loads while the phenomenon of stress concentration occurs at the edge of large Adhesion patches. As such, the effective stiffness of the FA-ECM complex that is either too small or too large will be relatively low, resulting in a limited actomyosin pulling force developed at the edge that is insufficient to prevent disassembly. Furthermore, it is found that a stiffer ECM and/or nucleus, as well as a stronger chemo-mechanical feedback, will induce larger Adhesions along with a higher level of contraction force. Interestingly, switching the extracellular side from an elastic half-space, corresponding to some widely used in vitro gel substrates, to a 1D fiber does not qualitative change these conclusions. Our model predictions are in good agreement with a variety of experimental observations obtained in this study as well as those reported in the literature. Furthermore, this new model provides a framework in which to understand how both intracellular and extracellular perturbations lead to changes in Adhesion Structure number and size.
-
a chemomechanical model of matrix and nuclear rigidity regulation of focal Adhesion size
Biophysical Journal, 2015Co-Authors: Tristian P Driscoll, Janusz Francobarraza, Edna Cukierman, Robert L Mauck, Vivek B ShenoyAbstract:In this work, a chemomechanical model describing the growth dynamics of cell-matrix Adhesion Structures (i.e., focal Adhesions (FAs)) is developed. We show that there are three regimes for FA evolution depending on their size. Specifically, nascent Adhesions with initial lengths below a critical value that are yet to engage in actin fibers will dissolve, whereas bigger ones will grow into mature FAs with a steady state size. In Adhesions where growth surpasses the steady state size, disassembly will occur until their sizes are reduced to the equilibrium state. This finding arises from the fact that polymerization of Adhesion proteins is force-dependent. Under actomyosin contraction, individual integrin bonds within small FAs (i.e., nascent Adhesions or focal complexes) must transmit higher loads while the phenomenon of stress concentration occurs at the edge of large Adhesion patches. As such, an effective stiffness of the FA-extracellular matrix complex that is either too small or too large will be relatively low, resulting in a limited actomyosin pulling force developed at the edge that is insufficient to prevent disassembly. Furthermore, it is found that a stiffer extracellular matrix and/or nucleus, as well as a stronger chemomechanical feedback, will induce larger Adhesions along with a higher level of contraction force. Interestingly, switching the extracellular side from an elastic half-space, corresponding to some widely used in vitro gel substrates, to a one-dimensional fiber (as in the case of cells anchoring to a fibrous scaffold in vivo) does not qualitative change these conclusions. Our model predictions are in good agreement with a variety of experimental observations obtained in this study as well as those reported in the literature. Furthermore, this new model, to our knowledge, provides a framework with which to understand how both intracellular and extracellular perturbations lead to changes in Adhesion Structure number and size.
Eva D. Martin - One of the best experts on this subject based on the ideXlab platform.
-
Plakoglobin expression and localization in zebrafish embryo development.
Biochemical Society Transactions, 2004Co-Authors: Eva D. Martin, Maura GrealyAbstract:Plakoglobin (γ-catenin) and β-catenin are major components of the adherens junctions and can be localized to the nucleus by activation of the Wnt signalling pathway. In addition, plakoglobin is also found in desmosomes, a vertebrate-specific cell–cell Adhesion Structure. Plakoglobin expression and localization were examined at the protein level during zebrafish embryonic development by Western blotting and confocal microscopy. Plakoglobin was expressed throughout embryo development at the protein level. Western blotting revealed that embryonic plakoglobin protein content increased between 12- and 24-h post-fertilization (hpf). Confocal microscopy showed that at stages up to 12 hpf, plakoglobin and β-catenin were co-localized and expressed in both the nucleus and in cell–cell junctions. At 24- and 72-hpf, separate patterns were seen for plakoglobin and β-catenin. These data indicate that plakoglobin localization in the heart region shifts from adherens junctions to desmosomes during heart chamber development.
-
Plakoglobin expression and localization in zebrafish embryo development.
Biochemical Society transactions, 2004Co-Authors: Eva D. Martin, Maura GrealyAbstract:Plakoglobin (gamma-catenin) and beta-catenin are major components of the adherens junctions and can be localized to the nucleus by activation of the Wnt signalling pathway. In addition, plakoglobin is also found in desmosomes, a vertebrate-specific cell-cell Adhesion Structure. Plakoglobin expression and localization were examined at the protein level during zebrafish embryonic development by Western blotting and confocal microscopy. Plakoglobin was expressed throughout embryo development at the protein level. Western blotting revealed that embryonic plakoglobin protein content increased between 12- and 24-h post-fertilization (hpf). Confocal microscopy showed that at stages up to 12 hpf, plakoglobin and beta-catenin were co-localized and expressed in both the nucleus and in cell-cell junctions. At 24- and 72-hpf, separate patterns were seen for plakoglobin and beta-catenin. These data indicate that plakoglobin localization in the heart region shifts from adherens junctions to desmosomes during heart chamber development.
Heiani Touaitahuata - One of the best experts on this subject based on the ideXlab platform.
-
tensin 3 is a new partner of dock5 that controls osteoclast podosome organization and activity
Journal of Cell Science, 2016Co-Authors: Heiani Touaitahuata, Julio Mateoslangerak, Sylvain De Rossi, Anne Morel, Serge UrbachAbstract:Bone resorption by osteoclasts is mediated by a typical Adhesion Structure called the sealing zone or actin ring, whose architecture is based on a belt of podosomes. The molecular mechanisms driving podosome organization into superStructures remain poorly understood to date, in particular at the osteoclast podosome belt. We performed proteomic analyses in osteoclasts and found that the adaptor protein tensin 3 is a partner of Dock5, a Rac exchange factor necessary for podosome belt formation and bone resorption. Expression of tensin 3 and Dock5 concomitantly increase during osteoclast differentiation. These proteins associate with the osteoclast podosome belt but not with individual podosomes, in contrast to vinculin. Super-resolution microscopy revealed that, even if they colocalize in the x-y plane of the podosome belt, Dock5 and tensin 3 differentially localize relative to vinculin in the z-axis. Tensin 3 increases Dock5 exchange activity towards Rac, and suppression of tensin 3 in osteoclasts destabilizes podosome organization, leading to delocalization of Dock5 and a severe reduction in osteoclast activity. Our results suggest that Dock5 and tensin 3 cooperate for osteoclast activity, to ensure the correct organization of podosomes.
-
Podosomes are dispensable for osteoclast differentiation and migration.
European journal of cell biology, 2013Co-Authors: Heiani Touaitahuata, Emmanuelle Planus, Corinne Albiges-rizo, Anne Blangy, Geraldine PawlakAbstract:Podosomes are Adhesion Structures characteristic of the myeloid cell lineage, encompassing osteoclasts, dendritic cells and macrophages. Podosomes are actin-based Structures that are dynamic and capable of self-organization. In particular in the osteoclast, podosomes densely pack into a thick ring called the sealing zone. This Adhesion Structure is typical of osteoclasts and necessary for the resorption of the bone matrix. We thought to explore in more details the role of podosomes during osteoclast differentiation and migration. To this end, we made from soft to stiff substrates that had not been functionalized with extracellular matrix proteins. Such substrates did not support podosome formation in osteoclasts. With such devices, we could show that integrin activation was sufficient to drive podosome assembly, in a substrate stiffness independent fashion. We additionally report here that osteoclast differentiation is a podosome-independent process. Finally, we show that osteoclasts devoid of podosomes can migrate efficiently. Our study further illustrates the great capacity of myeloid cells to adapt to the different environments they encounter during their life cycle.
Geraldine M. O'neill - One of the best experts on this subject based on the ideXlab platform.
-
Tropomyosin isoform modulation of focal Adhesion Structure and cell migration
Cell adhesion & migration, 2010Co-Authors: Cuc T.t. Bach, Galina Schevzov, Nicole S. Bryce, Peter W. Gunning, Geraldine M. O'neillAbstract:Orderly cell migration is essential for embryonic development, efficient wound healing and a functioning immune system and the dysregulation of this process leads to a number of pathologies. The speed and direction of cell migration is critically dependent on the structural organization of focal Adhesions in the cell. While it is well established that contractile forces derived from the acto-myosin filaments control the Structure and growth of focal Adhesions, how this may be modulated to give different outcomes for speed and persistence is not well understood. The tropomyosin family of actin-associating proteins are emerging as important modulators of the contractile nature of associated actin filaments. The multiple non-muscle tropomyosin isoforms are differentially expressed between tissues and across development and are thought to be major regulators of actin filament functional specialization. In the present study we have investigated the effects of two splice variant isoforms from the same alpha-tropomyosin gene, TmBr1 and TmBr3, on focal Adhesion Structure and parameters of cell migration. These isoforms are normally switched on in neuronal cells during differentiation and we find that exogenous expression of the two isoforms in undifferentiated neuronal cells has discrete effects on cell migration parameters. While both isoforms cause reduced focal Adhesion size and cell migration speed, they differentially effect actin filament phenotypes and migration persistence. Our data suggests that differential expression of tropomyosin isoforms may coordinate acto-myosin contractility and focal Adhesion Structure to modulate cell speed and persistence.
-
Cytoskeletal regulation of focal Adhesion Structure: A mechanism to control cell migration.
Cancer Research, 2007Co-Authors: Cuc T.t. Bach, Peter W. Gunning, Jessie Zhong, Lauren Cowell, Geraldine M. O'neillAbstract:3033 Two core components in cell migration are the actin cytoskeleton and integrin-based Adhesion to the extra-cellular matrix, known as focal Adhesions (FAs). FA turnover allows cells to move over the underlying matrix while the actin cytoskeleton directly links to the FAs providing the contractile force that generates movement. Actin filament Structure is regulated by distinct isoforms of the tropomyosin (Tm) family of actin-binding proteins. Given the key relationship between Adhesion and actin in cell migration, we hypothesized that Tm isoform expression may regulate Adhesion Structure, in turn determining downstream signalling and migration. To test our hypothesis we have employed B35 rat cells overexpressing the Tm isoform Tm5NM1 and mouse embryo fibroblasts (MEFs) derived from a Tm5NM1 knockout mouse model. Using time-lapse microscopy we determined that cells expressing Tm5NM1 display reduced random cell movement, while the Tm5NM1 -/- MEFs travel significantly further than controls. Notably, the velocity of the wild-type and knockout MEFs is identical, therefore suggesting that the Tm5NM1 -/- MEFs may be more polarized. Cells overexpressing Tm5NM1 display FAs that are twice the length of control cells and are dispersed across the ventral surface of the cell. In contrast, Tm5NM1 -/- MEFs display enhanced levels of pre-cursor Adhesion formation arrayed at the leading edge of protruding membranes. To investigate why the FAs are larger in the Tm5NM1 overexpressing cells we have measured Adhesion dynamics. The data demonstrate that the FAs are significantly stabilized in the Tm5NM1-expressing cells. Further the stabilization of FAs in Tm5NM1-expressing cells appears to require the presence of polymerized actin as treatment with the actin-destabilizing agent latrunculin correspondingly promotes FA turnover. We have begun to investigate how altered Adhesion Structure might impact integrin-mediated signalling pathways and our preliminary data indicate that the FA docking molecule p130Cas exhibits altered phosphorylation in the Tm5NM1 overexpressing cells. In a correlated finding we also observe decreased expression of the tyrosine kinase Src in these cells. Conversely, p130Cas phosphorylation and Src expression levels are unaltered in Tm5NM1-/- MEFs. Collectively, our data support Tm isoform-specific effects on FA Structure, Adhesion molecule activation and cell migration.
