scholarly journals A polarized nucleus-cytoskeleton-ECM connection controls collective migration and cardioblasts number in Drosophila

2019 ◽  
Author(s):  
C Dondi ◽  
B Bertin ◽  
JP Da Ponte ◽  
I Wojtowicz ◽  
K Jagla ◽  
...  
Keyword(s):  
Focal Adhesion ◽  
Cardiac Cells ◽  
Collective Migration ◽  
Molecular Processes ◽  
Directional Migration ◽  
Lumen Formation ◽  
Adhesion Sites ◽  
Spatial Expression Pattern ◽  
Temporal And Spatial ◽  
Made In

AbstractThe formation of the cardiac tube is a remarkable example of complex morphogenetic process conserved from invertebrates to humans. It involves coordinated collective migration of contralateral rows of cardiac cells. The molecular processes underlying the specification of cardioblasts prior to migration are well established and significant advances have been made in understanding the process of lumen formation. However, the mechanisms of collective cardiac cells migration remain elusive. Here we identified CAP and MSP-300 as novel actors involved in cardioblast migration. They both display highly similar temporal and spatial expression pattern in migrating cardiac cells and are required for the correct number, alignment and coordinated directional migration of cardioblasts. Our data suggest that CAP and MSP-300 are part of a tension-sensitive protein complex linking cardioblast focal adhesion sites to nuclei via actin cytoskeleton and triggering coordinated cardioblast movements.

scholarly journals A polarized nucleus-cytoskeleton-ECM connection in migrating cardioblasts controls heart tube formation

Development ◽  
2021 ◽  
Author(s):  
Cristiana Dondi ◽  
Benjamin Bertin ◽  
Jean-Philippe Daponte ◽  
Inga Wojtowicz ◽  
Krzysztof Jagla ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Tube Formation ◽  
Cardiac Cells ◽  
Collective Migration ◽  
Heart Tube ◽  
Adhesion Sites ◽  
Correct Alignment ◽  
Temporal And Spatial ◽  
Heart Tube Formation ◽  
Made In

The formation of the cardiac tube is a remarkable example of complex morphogenetic processes conserved from invertebrates to humans. It involves coordinated collective migration of contralateral rows of cardiac cells. The molecular processes underlying the specification of cardioblasts (CBs) prior to migration are well established and significant advances have been made in understanding the process of lumen formation. However, the mechanisms of collective cardiac cells migration remain elusive. Here we identified CAP and MSP300 as novel actors involved during CBs migration. They both exhibit highly similar temporal and spatial expression patterns in migrating cardiac cells and are necessary for the correct number and alignment of CBs, a prerequisite for the coordination of their collective migration. Our data suggest that CAP and MSP300 are part of a protein complex linking focal adhesion sites to nuclei via the actin cytoskeleton that maintains post-mitotic state and correct alignment of CBs.

scholarly journals Caspase-mediated Cleavage of p130cas in Etoposide-induced Apoptotic Rat-1 Cells

2000 ◽  
Vol 11 (3) ◽  
pp. 929-939 ◽  
Author(s):  
Seunghyi Kook ◽  
Sang Ryeol Shim ◽  
Soo Jeon Choi ◽  
Joohong Ahnn ◽  
Jae Il Kim ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Focal Adhesion ◽  
Caspase 3 ◽  
Morphological Changes ◽  
Point Mutations ◽  
Membrane Blebbing ◽  
Adhesion Sites ◽  
Focal Adhesion Proteins ◽  
Induced Apoptosis

Apoptosis causes characteristic morphological changes in cells, including membrane blebbing, cell detachment from the extracellular matrix, and loss of cell–cell contacts. We investigated the changes in focal adhesion proteins during etoposide-induced apoptosis in Rat-1 cells and found that during apoptosis, p130cas (Crk-associated substrate [Cas]) is cleaved by caspase-3. Sequence analysis showed that Cas contains 10 DXXD consensus sites preferred by caspase-3. We identified two of these sites (DVPD416G and DSPD748G) in vitro, and point mutations substituting the Asp of DVPD416G and DSPD748G with Glu blocked caspase-3-mediated cleavage. Cleavage at DVPD416G generated a 74-kDa fragment, which was in turn cleaved at DSPD748G, yielding 47- and 31-kDa fragments. Immunofluorescence microscopy revealed well-developed focal adhesion sites in control cells that dramatically declined in number in etoposide-treated cells. Cas cleavage correlated temporally with the onset of apoptosis and coincided with the loss of p125FAK (focal adhesion kinase [FAK]) from focal adhesion sites and the attenuation of Cas–paxillin interactions. Considering that Cas associates with FAK, paxillin, and other molecules involved in the integrin signaling pathway, these results suggest that caspase-mediated cleavage of Cas contributes to the disassembly of focal adhesion complexes and interrupts survival signals from the extracellular matrix.

Integrin subunits (beta)1C-1 and (beta)1C-2 expressed in GD25T cells are retained and degraded intracellularly rather than localised to the cell surface

1999 ◽  
Vol 112 (24) ◽  
pp. 4751-4761
Author(s):  
G. Svineng ◽  
S. Johansson
Keyword(s):  
Cell Surface ◽  
Focal Adhesion ◽  
Northern Blot Analysis ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Deficient Mouse ◽  
Normal Cells ◽  
Alpha Subunits ◽  
Metabolic Labelling ◽  
Adhesion Sites

We have previously identified the integrin (beta)1C-2 and characterised the distribution of (beta)1C-1 and (beta)1C-2 transcripts in various cell lines and normal cells. In this study we have investigated the expression of the two (beta)1C-variants in integrin (beta)1 deficient mouse GD25T cells. After stable transfection of the GD25T cells with cDNAs coding for (beta)1A, (beta)1C-1 and (beta)1C-2, the cell surface expression of the (beta)1C-1 and (beta)1C-2 variants was found to be very low while the (beta)1A variant was expressed at high levels. Northern blot analysis showed that the level of (beta)1-transcript in the (beta)1C-1 and (beta)1C-2 clones was equal or higher than in the (beta)1A clones. Metabolic labelling and deglycosylation by endoglycosidase H treatment clearly demonstrated that the majority of the (beta)1C-1 and (beta)1C-2 chains did not become maturely glycosylated, nor did they dimerize with (alpha) subunits. After 20 hours of chase, the labelled (beta)1C-1 and (beta)1C-2 chains had been gradually degraded, whereas immature (beta)1A was converted into the maturely glycosylated form during the same period of time. Immunostaining showed intracellular (beta)1 localisation in the (beta)1C-1 and (beta)1C-2 expressing clones, while in the (beta)1A expressing clones the (beta)1 chains were mainly localised to focal adhesion sites and along fibronectin fibres. Taken together, we have shown that expression of both integrin (beta)1C-1 and (beta)1C-2 in GD25T cells result in very low cell surface expression compared with the normal (beta)1A isoform. Instead, both (beta)1C-1 and (beta)1C-2 chains remain in the endoplasmic reticulum until they are intracellularly degraded.

Learning from cerebellar lesions about the temporal and spatial aspects of saccadic control

1999 ◽  
Vol 22 (4) ◽  
pp. 687-688
Author(s):  
Alain Guillaume ◽  
Laurent Goffart ◽  
Denis Pélisson
Keyword(s):  
Saccadic Eye Movements ◽  
The Other ◽  
Parallel Processes ◽  
Pathological Conditions ◽  
Cerebellar Lesions ◽  
Temporal And Spatial ◽  
Winner Take All ◽  
Salience Map ◽  
Made In ◽  
Take All

In the model proposed by Findlay & Walker, the programming of saccadic eye movements is achieved by two parallel processes, one dedicated to the coding of saccade metrics (Where) and the other controlling saccade initiation (When). One outcome of the “winner-take-all” characteristics of the salience map, the main node of the model, is an independence between the metrics and the latency of saccades. We report on some observations, made in the head-unrestrained cat under pathological conditions, of a correlation between accuracy and latency of saccadic gaze shifts. To account for such a correlation, the link between metrics specification (Where) and saccade triggering (When) should be amended in the model.

scholarly journals Cells of the adult human heart

Nature ◽  
2020 ◽  
Vol 588 (7838) ◽  
pp. 466-472 ◽  
Author(s):  
Monika Litviňuková ◽  
Carlos Talavera-López ◽  
Henrike Maatz ◽  
Daniel Reichart ◽  
Catherine L. Worth ◽  
...  
Keyword(s):  
Human Heart ◽  
Large Scale ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cardiac Cells ◽  
Cellular Heterogeneity ◽  
Molecular Processes ◽  
Future Studies ◽  
Disease Mechanisms ◽  
Single Nucleus

AbstractCardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies.

Force-induced focal adhesion translocation: effects of force amplitude and frequency

2004 ◽  
Vol 287 (4) ◽  
pp. C954-C962 ◽  
Author(s):  
P. J. Mack ◽  
M. R. Kaazempur-Mofrad ◽  
H. Karcher ◽  
R. T. Lee ◽  
R. D. Kamm
Keyword(s):  
Tyrosine Kinase ◽  
Focal Adhesion ◽  
Magnetic Beads ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Apical Cell ◽  
Force Transmission ◽  
Shear Forces ◽  
Apical Cell Membrane ◽  
Adhesion Sites

Vascular endothelial cells rapidly transduce local mechanical forces into biological signals through numerous processes including the activation of focal adhesion sites. To examine the mechanosensing capabilities of these adhesion sites, focal adhesion translocation was monitored over the course of 5 min with GFP-paxillin while applying nN-level magnetic trap shear forces to the cell apex via integrin-linked magnetic beads. A nongraded steady-load threshold for mechanotransduction was established between 0.90 and 1.45 nN. Activation was greatest near the point of forcing (<7.5 μm), indicating that shear forces imposed on the apical cell membrane transmit nonuniformly to the basal cell surface and that focal adhesion sites may function as individual mechanosensors responding to local levels of force. Results from a continuum, viscoelastic finite element model of magnetocytometry that represented experimental focal adhesion attachments provided support for a nonuniform force transmission to basal surface focal adhesion sites. To further understand the role of force transmission on focal adhesion activation and dynamics, sinusoidally varying forces were applied at 0.1, 1.0, 10, and 50 Hz with a 1.45 nN offset and a 2.25 nN maximum. At 10 and 50 Hz, focal adhesion activation did not vary with spatial location, as observed for steady loading, whereas the response was minimized at 1.0 Hz. Furthermore, applying the tyrosine kinase inhibitors genistein and PP2, a specific Src family kinase inhibitor, showed tyrosine kinase signaling has a role in force-induced translocation. These results highlight the mutual importance of force transmission and biochemical signaling in focal adhesion mechanotransduction.

Laminin Binding Conveys Mechanosensing in Endothelial Cells

Physiology ◽  
2002 ◽  
Vol 17 (4) ◽  
pp. 166-169 ◽  
Author(s):  
Torsten Gloe ◽  
Ulrich Pohl
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Focal Adhesion ◽  
Binding Protein ◽  
Signaling Cascades ◽  
Adhesion Sites ◽  
Receptor Kinases ◽  
Laminin Binding Protein ◽  
Laminin Binding

In endothelial cells, forces like shear stress are transferred to focal adhesion sites and activate in concert with matrix receptor kinases, leading to an initiation of signaling cascades. The laminin binding protein is one of these matrix receptors and is critically involved in sensing and quantification of shear stress.

Study of Cellular Adhesion by Means of Micropillar Surface Topologies

2011 ◽  
Vol 409 ◽  
pp. 105-110 ◽  
Author(s):  
Francesca Boccafoschi ◽  
Marco Rasponi ◽  
Cecilia Mosca ◽  
Erica Bocchi ◽  
Simone Vesentini
Keyword(s):  
Focal Adhesion ◽  
Vascular Tissue ◽  
Focal Adhesions ◽  
Traction Force ◽  
Cellular Adhesion ◽  
Research Field ◽  
Traction Forces ◽  
Adhesion Sites ◽  
Substrate Rigidity ◽  
Open Question

It is well-known that cellular behavior can be guided by chemical signals and physical interactions at the cell-substrate interface. The patterns that cells encounter in their natural environment include nanometer-to-micrometer-sized topographies comprising extracellular matrix, proteins, and adjacent cells. Whether cells transduce substrate rigidity at the microscopic scale (for example, sensing the rigidity between adhesion sites) or the nanoscopic scale remains an open question. Here we report that micromolded elastomeric micropost arrays can decouple substrate rigidity from adhesive and surface properties. Arrays of poly (dimethylsiloxane) (PDMS) microposts from microfabricated silicon masters have been fabricated. To control substrate rigidity they present the same post heights but different surface area and spacing between posts. The main advantage of micropost arrays over other surface modification solutions (i.e. hydrogels) is that measured subcellular traction forces could be attributed directly to focal adhesions. This would allow to map traction forces to individual focal adhesions and spatially quantify subcellular distributions of focal-adhesion area, traction force and focal-adhesion stress. Moreover, different adhesion intracellular pathways could be used by the cells to differentiate toward a proliferative or a contractile cellular phenotype, for instance. This particular application is advantageous for vascular tissue engineering applications, where mimicking as close as possible the vessels dynamics should be a step forward in this research field.

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