scholarly journals Spatial integration of mechanical forces by alpha-actinin establishes actin network symmetry

2019 ◽  
Author(s):  
Fabrice Senger ◽  
Amandine Pitaval ◽  
Hajer Ennomani ◽  
Laetitia Kurzawa ◽  
Laurent Blanchoin ◽  
...  

Cell and tissue morphogenesis depend on the production and spatial organization of tensional forces in the actin cytoskeleton. Actin network architecture is complex because it is made of distinct modules in which filaments adopt a variety of organizations. The assembly and dynamics of these modules is well described but the self-organisation rules directing the global network architecture are much less understood. Here we investigated the mechanism regulating the interplay between network architecture and the geometry of cell’s extracellular environment. We found that α-actinin, a filament crosslinker, is essential for network symmetry to be consistent with extracellular microenvironment symmetry. It appeared to be required for the interconnection of transverse arcs with radial fibres to ensure an appropriate balance between forces at cell adhesions and across the entire actin network. Furthermore, the connectivity of the actin network appeared necessary for the cell ability to integrate and adapt to complex patterns of extracellular cues as they migrate. Altogether, our study has unveiled a role of actin-filament crosslinking in the physical integration of mechanical forces throughout the entire cell, and the role of this integration in the establishment and adaptation of intracellular symmetry axes in accordance with the geometry of extracellular cues.

2014 ◽  
Vol 306 (6) ◽  
pp. C607-C620 ◽  
Author(s):  
Hiroaki Hirata ◽  
Hitoshi Tatsumi ◽  
Chwee Teck Lim ◽  
Masahiro Sokabe

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.


2021 ◽  
Vol 220 (5) ◽  
Author(s):  
Yanling Yan ◽  
Shuai Liu ◽  
Can Hu ◽  
Chaoyi Xie ◽  
Linyue Zhao ◽  
...  

Cargo sorting and the subsequent membrane carrier formation require a properly organized endosomal actin network. To better understand the actin dynamics during endocytic recycling, we performed a genetic screen in C. elegans and identified RTKN-1/Rhotekin as a requisite to sustain endosome-associated actin integrity. Loss of RTKN-1 led to a prominent decrease in actin structures and basolateral recycling defects. Furthermore, we showed that the presence of RTKN-1 thwarts the actin disassembly competence of UNC-60A/cofilin. Consistently, in RTKN-1–deficient cells, UNC-60A knockdown replenished actin structures and alleviated the recycling defects. Notably, an intramolecular interaction within RTKN-1 could mediate the formation of oligomers. Overexpression of an RTKN-1 mutant form that lacks self-binding capacity failed to restore actin structures and recycling flow in rtkn-1 mutants. Finally, we demonstrated that SDPN-1/Syndapin acts to direct the recycling endosomal dwelling of RTKN-1 and promotes actin integrity there. Taken together, these findings consolidated the role of SDPN-1 in organizing the endosomal actin network architecture and introduced RTKN-1 as a novel regulatory protein involved in this process.


2019 ◽  
Vol 132 (22) ◽  
pp. jcs236604 ◽  
Author(s):  
Fabrice Senger ◽  
Amandine Pitaval ◽  
Hajer Ennomani ◽  
Laetitia Kurzawa ◽  
Laurent Blanchoin ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Danlin Shen ◽  
Qing Li ◽  
Jianmei Liu ◽  
Yi Liao ◽  
Yuanyuan Li ◽  
...  

Background: Schizophrenia is associated with a significant increase in the risk of violence, which constitutes a public health concern and contributes to stigma associated with mental illness. Although previous studies revealed structural and functional abnormalities in individuals with violent schizophrenia (VSZ), the neural basis of psychotic violence remains controversial.Methods: In this study, high-resolution structural magnetic resonance imaging (MRI) data were acquired from 18 individuals with VSZ, 23 individuals with non-VSZ (NSZ), and 22 age- and sex-matched healthy controls (HCs). Whole-brain voxel-based morphology and individual morphological covariance networks were analysed to reveal differences in gray matter volume (GMV) and individual morphological covariance network topology. Relationships among abnormal GMV, network topology, and clinical assessments were examined using correlation analyses.Results: GMV in the hypothalamus gradually decreased from HCs and NSZ to VSZ and showed significant differences between all pairs of groups. Graph theory analyses revealed that morphological covariance networks of HCs, NSZ, and VSZ exhibited small worldness. Significant differences in network topology measures, including global efficiency, shortest path length, and nodal degree, were found. Furthermore, changes in GMV and network topology were closely related to clinical performance in the NSZ and VSZ groups.Conclusions: These findings revealed the important role of local structural abnormalities of the hypothalamus and global network topological impairments in the neuropathology of NSZ and VSZ, providing new insight into the neural basis of and markers for VSZ and NSZ to facilitate future accurate clinical diagnosis and targeted treatment.


2021 ◽  
Vol 15 ◽  
Author(s):  
Enrico Collantoni ◽  
Paolo Meneguzzo ◽  
Elena Tenconi ◽  
Valentina Meregalli ◽  
Renzo Manara ◽  
...  

No study to date investigated structural white matter (WM) connectome characteristics in patients with anorexia nervosa (AN). Previous research in AN found evidence of imbalances in global and regional connectomic brain architecture and highlighted a role of malnutrition in determining structural brain changes. The aim of our study was to explore the characteristics of the WM network architecture in a sample of patients with AN. Thirty-six patients with AN and 36 healthy women underwent magnetic resonance imaging to obtain a high-resolution three-dimensional T1-weighted anatomical image and a diffusion tensor imaging scan. Probabilistic tractography data were extracted and analyzed in their network properties through graph theory tools. In comparison to healthy women, patients with AN showed lower global network segregation (normalized clustering: p = 0.029), an imbalance between global network integration and segregation (i.e., lower small-worldness: p = 0.031), and the loss of some of the most integrative and influential hubs. Both clustering and small-worldness correlated with the lowest lifetime body mass index. A significant relationship was found between the average regional loss of cortical volume and changes in network properties of brain nodes: the more the difference in the cortical volume of brain areas, the more the increase in the centrality of corresponding nodes in the whole brain, and the decrease in clustering and efficiency of the nodes of parietal cortex. Our findings showed an unbalanced connectome wiring in AN patients, which seems to be influenced by malnutrition and loss of cortical volume. The role of this rearrangement in the maintenance and prognosis of AN and its reversibility with clinical improvement needs to be established by future studies.


2010 ◽  
Vol 1274 ◽  
Author(s):  
Taher Saif ◽  
Jagannathan Rajagopalan ◽  
Alireza Tofangchi

AbstractWe used high resolution micromechanical force sensors to study the in vivo mechanical response of embryonic Drosophila neurons. Our experiments show that Drosophila axons have a rest tension of a few nN and respond to mechanical forces in a manner characteristic of viscoelastic solids. In response to fast externally applied stretch they show a linear force-deformation response and when the applied stretch is held constant the force in the axons relaxes to a steady state value over time. More importantly, when the tension in the axons is suddenly reduced by releasing the external force the neurons actively restore the tension, sometimes close to their resting value. Along with the recent findings of Siechen et al (Proc. Natl. Acad. Sci. USA 106, 12611 (2009)) showing a link between mechanical tension and synaptic plasticity, our observation of active tension regulation in neurons suggest an important role for mechanical forces in the functioning of neurons in vivo.


2017 ◽  
Vol 39 (8) ◽  
pp. 1194-1209 ◽  
Author(s):  
Marwan M Kraidy

Islamic State’s (IS) image-warfare presents an auspicious opportunity to grasp the growing role of digital images in emerging configurations of global conflict. To understand IS’ image-warfare, this article explores the central role of digital images in the group’s war spectacle and identifies a key modality of this new kind of warfare: global networked affect. To this end, the analysis focuses on three primary sources: two Arabic-language IS books, Management of Savagery (2004) and O’ Media Worker, You Are a Mujahid!, 2nd Edition (2016), and a video, Healing the Believers’ Chests (2015), featuring the spectacular burning of a Jordanian air force pilot captured by IS. It uses the method of ‘iconology’ within a case-study approach. I analyze IS’ doctrine of image-warfare explained in the two books and, in turn, examine how this doctrine is executed in IS video production, conceptualizing digital video as a specific permutation of moving digital images uniquely able to enact, and via repetition, to maintain, visual and narrative tension between movement and stillness, speed and slowness, that diffuses global network affect. Using a theoretical framework combining spectacle, new media phenomenology, and affect theory, the article concludes that global networked affect is projectilic, mimicking fast, lethal, penetrative objects. IS visual warfare, I argue, is best understood through the notion of the ‘projectilic image’.


2017 ◽  
Vol 31 (1) ◽  
pp. 84-92
Author(s):  
Celio M. Lopes ◽  
Flora Misaki ◽  
Karina Santos ◽  
Carlos A. P. Evangelista ◽  
Tatiana T. Carrijo ◽  
...  

2014 ◽  
Vol 10 ◽  
pp. P383-P384 ◽  
Author(s):  
Michael J. O'Sullivan ◽  
Rok Berlot ◽  
Claudia Metzler-Baddeley ◽  
Nicola J. Ray ◽  
Derek K. Jones ◽  
...  

2019 ◽  
Vol 29 (39) ◽  
pp. 1903114 ◽  
Author(s):  
Ali Doryab ◽  
Sinem Tas ◽  
Mehmet Berat Taskin ◽  
Lin Yang ◽  
Anne Hilgendorff ◽  
...  

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