Push or pull: how cytoskeletal crosstalk facilitates nuclear movement through 3D environments

2021 ◽  
Author(s):  
Pragati Marks ◽  
Ryan Petrie
Keyword(s):  
Protein Complexes ◽  
Focal Adhesions ◽  
Nuclear Migration ◽  
Two Dimensional ◽  
Nuclear Movement ◽  
3D Environments ◽  
Cytoskeletal Networks ◽  
3D Cell Migration ◽  
Molecular Crosstalk

Abstract As cells move from two-dimensional (2D) surfaces into complex 3D environments, the nucleus becomes a barrier to movement due to its size and rigidity. Therefore, moving the nucleus is a key step in 3D cell migration. In this review, we discuss how coordination between cytoskeletal and nucleoskeletal networks is required to pull the nucleus forward through complex 3D spaces. We summarize recent migration models which utilize unique molecular crosstalk to drive nuclear migration through different 3D environments. In addition, we speculate about the role of proteins that indirectly crosslink cytoskeletal networks and the role of 3D focal adhesions and how these protein complexes may drive 3D nuclear migration.

scholarly journals Cell migration: Fibroblasts find a new way to get ahead

2012 ◽  
Vol 197 (3) ◽  
pp. 347-349 ◽  
Author(s):  
Michael Sixt
Keyword(s):  
Cell Migration ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Two Dimensional ◽  
Tissue Explants ◽  
Cell Biol ◽  
Membrane Blebs ◽  
3D Environments ◽  
Actomyosin Contraction ◽  
Phosphatidylinositol 3

Fibroblasts migrate on two-dimensional (2D) surfaces by forming lamellipodia—actin-rich extensions at the leading edge of the cell that have been well characterized. In this issue, Petrie et al. (2012. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201201124) show that in some 3D environments, including tissue explants, fibroblasts project different structures, termed lobopodia, at the leading edge. Lobopodia still assemble focal adhesions; however, similar to membrane blebs, they are driven by actomyosin contraction and do not accumulate active Rac, Cdc42, and phosphatidylinositol 3-kinases.

Focal adhesions are involved in simulated-microgravity-induced basilar and femoral arterial remodelling in rats

2018 ◽  
Vol 96 (8) ◽  
pp. 772-782 ◽  
Author(s):  
Min Jiang ◽  
Qiang Lyu ◽  
Yun-Gang Bai ◽  
Huan Liu ◽  
Jing Yang ◽  
...  
Keyword(s):  
Basilar Artery ◽  
Femoral Artery ◽  
Simulated Microgravity ◽  
Orthostatic Intolerance ◽  
Protein Complexes ◽  
Focal Adhesions ◽  
Femoral Arteries ◽  
Haemodynamic Changes ◽  
Structural Adaptations

Recent studies have suggested that microgravity-induced arterial remodelling contributes to post-flight orthostatic intolerance and that multiple mechanisms are involved in arterial remodelling. However, the initial mechanism by which haemodynamic changes induce arterial remodelling is unknown. Focal adhesions (FAs) are dynamic protein complexes that have mechanotransduction properties. This study aimed to investigate the role of FAs in simulated-microgravity-induced basilar and femoral arterial remodelling. A 4-week hindlimb-unweighted (HU) rat model was used to simulate the effects of microgravity, and daily 1-hour intermittent artificial gravity (IAG) was used to prevent arterial remodelling. After 4-week HU, wall thickness, volume of smooth muscle cells (SMCs) and collagen content were increased in basilar artery but decreased in femoral artery (P < 0.05). Additionally, the expression of p-FAK Y397 and p-Src Y418 was increased and reduced in SMCs of basilar and femoral arteries, respectively, by HU (P < 0.05). The number of FAs was increased in basilar artery and reduced in femoral artery by HU (P < 0.05). Furthermore, daily 1-hour IAG prevented HU-induced differential structural adaptations and changes in FAs of basilar and femoral arteries. These results suggest that FAs may act as mechanosensors in arterial remodelling by initiating intracellular signal transduction in response to altered mechanical stress induced by microgravity.

scholarly journals Investigating lasp-2 in cell adhesion: new binding partners and roles in motility

2013 ◽  
Vol 24 (7) ◽  
pp. 995-1006 ◽  
Author(s):  
Katherine T. Bliss ◽  
Miensheng Chu ◽  
Colin M. Jones-Weinert ◽  
Carol C. Gregorio
Keyword(s):  
Focal Adhesion ◽  
Cell Attachment ◽  
Protein Complexes ◽  
Metastatic Cancer ◽  
Focal Adhesions ◽  
Actin Binding ◽  
Binding Partners ◽  
Focal Adhesion Proteins ◽  
Metastatic Cancer Cell

Focal adhesions are intricate protein complexes that facilitate cell attachment, migration, and cellular communication. Lasp-2 (LIM-nebulette), a member of the nebulin family of actin-binding proteins, is a newly identified component of these complexes. To gain further insights into the functional role of lasp-2, we identified two additional binding partners of lasp-2: the integral focal adhesion proteins vinculin and paxillin. Of interest, the interaction of lasp-2 with its binding partners vinculin and paxillin is significantly reduced in the presence of lasp-1, another nebulin family member. The presence of lasp-2 appears to enhance the interaction of vinculin and paxillin with each other; however, as with the interaction of lasp-2 with vinculin or paxillin, this effect is greatly diminished in the presence of excess lasp-1. This suggests that the interplay between lasp-2 and lasp-1 could be an adhesion regulatory mechanism. Lasp-2’s potential role in metastasis is revealed, as overexpression of lasp-2 in either SW620 or PC-3B1 cells—metastatic cancer cell lines—increases cell migration but impedes cell invasion, suggesting that the enhanced interaction of vinculin and paxillin may functionally destabilize focal adhesion composition. Taken together, these data suggest that lasp-2 has an important role in coordinating and regulating the composition and dynamics of focal adhesions.

scholarly journals Hyperthermia induced disruption of mechanical balance leads to G1 arrest and senescence in cells

2020 ◽  
Author(s):  
Nikita Mundhara ◽  
Abhijit Majumder ◽  
Dulal Panda
Keyword(s):  
Heat Stress ◽  
Prolonged Exposure ◽  
Heat Stroke ◽  
Focal Adhesions ◽  
Mitotic Cell ◽  
G1 Arrest ◽  
Cell Rounding ◽  
Cytoskeletal Networks ◽  
Mitotic Cells

Human body temperature limits below 40 °C during heat stroke or fever. The implications of prolonged exposure to the physiologically relevant temperature (40 °C) on cellular mechanobiology is poorly understood. Here, we have examined the effects of heat stress (40 °C for 72 h incubation) in human lung adenocarcinoma (A549), mouse melanoma (B16F10), and non-cancerous mouse origin adipose tissue cells (L929). Hyperthermia increased the level of ROS, γ-H2AX, and HSP70 and decreased mitochondrial membrane potential in the cells. Heat stress impaired cell division, caused G1 arrest, induced cellular senescence, and apoptosis in all the tested cell lines. The cells incubated at 40 °C for 72 h displayed a significant decrease in the f-actin level and cellular traction as compared to cells incubated at 37 °C. Also, the cells showed a larger focal adhesion area and stronger adhesion at 40 °C than at 37 °C. The mitotic cells at 40 °C were unable to round up properly and displayed retracting actin stress fibers. Hyperthermia downregulated HDAC6, increased the acetylation level of microtubules, and perturbed the chromosome alignment in the mitotic cells at 40 °C. Overexpression of HDAC6 rescued the cells from the G1 arrest and reduced the delay in cell rounding at 40 °C suggesting a crucial role of HDAC6 in hyperthermia mediated responses. This study elucidates the significant role of cellular traction, focal adhesions, and cytoskeletal networks in mitotic cell rounding and chromosomal misalignment. It also highlights the significance of HDAC6 in heat-evoked senile cellular responses.

scholarly journals EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 388
Author(s):  
Brice Chanez ◽  
Kevin Ostacolo ◽  
Ali Badache ◽  
Sylvie Thuault
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Focal Adhesions ◽  
Matrix Degradation ◽  
Cancer Cell Invasion ◽  
Wild Type ◽  
Spatial Regulation ◽  
Invadopodia Formation

Regulation of microtubule dynamics by plus-end tracking proteins (+TIPs) plays an essential role in cancer cell migration. However, the role of +TIPs in cancer cell invasion has been poorly addressed. Invadopodia, actin-rich protrusions specialized in extracellular matrix degradation, are essential for cancer cell invasion and metastasis, the leading cause of death in breast cancer. We, therefore, investigated the role of the End Binding protein, EB1, a major hub of the +TIP network, in invadopodia functions. EB1 silencing increased matrix degradation by breast cancer cells. This was recapitulated by depletion of two additional +TIPs and EB1 partners, APC and ACF7, but not by the knockdown of other +TIPs, such as CLASP1/2 or CLIP170. The knockdown of Focal Adhesion Kinase (FAK) was previously proposed to similarly promote invadopodia formation as a consequence of a switch of the Src kinase from focal adhesions to invadopodia. Interestingly, EB1-, APC-, or ACF7-depleted cells had decreased expression/activation of FAK. Remarkably, overexpression of wild type FAK, but not of FAK mutated to prevent Src recruitment, prevented the increased degradative activity induced by EB1 depletion. Overall, we propose that EB1 restricts invadopodia formation through the control of FAK and, consequently, the spatial regulation of Src activity.

scholarly journals Possible Protective Role of Melatonin in Pediatric Infectious Diseases and Neurodevelopmental Pathologies

2020 ◽  
Vol 10 (01) ◽  
pp. e104-e109
Author(s):  
Antonio Molina-Carballo ◽  
Antonio Emilio Jerez-Calero ◽  
Antonio Muñoz-Hoyos
Keyword(s):  
Endothelial Cell ◽  
Free Radical ◽  
Chronic Administration ◽  
Protective Role ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Energetic Metabolism ◽  
Beneficial Effects ◽  
Molecular Crosstalk

AbstractMelatonin, produced in every cell that possesses mitochondria, acts as an endogenous free radical scavenger, and improves energetic metabolism and immune function, by complex molecular crosstalk with other intracellular compounds. There is greatly increasing evidence regarding beneficial effects of acute and chronic administration of high melatonin doses, in infectious, developmental, and degenerative pathologies, as an endothelial cell and every cell protectant.

scholarly journals Mitochondrial microRNAs: A Putative Role in Tissue Regeneration

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 486
Author(s):  
Sílvia C. Rodrigues ◽  
Renato M. S. Cardoso ◽  
Filipe V. Duarte
Keyword(s):  
Tissue Regeneration ◽  
Protein Complexes ◽  
Mitochondrial Protein ◽  
Noncoding Rnas ◽  
Atp Synthesis ◽  
Mitochondrial Proteins ◽  
Cellular Mechanisms ◽  
Small Noncoding Rnas ◽  
Mitochondrial Ribosome

The most famous role of mitochondria is to generate ATP through oxidative phosphorylation, a metabolic pathway that involves a chain of four protein complexes (the electron transport chain, ETC) that generates a proton-motive force that in turn drives the ATP synthesis by the Complex V (ATP synthase). An impressive number of more than 1000 mitochondrial proteins have been discovered. Since mitochondrial proteins have a dual genetic origin, it is predicted that ~99% of these proteins are nuclear-encoded and are synthesized in the cytoplasmatic compartment, being further imported through mitochondrial membrane transporters. The lasting 1% of mitochondrial proteins are encoded by the mitochondrial genome and synthesized by the mitochondrial ribosome (mitoribosome). As a result, an appropriate regulation of mitochondrial protein synthesis is absolutely required to achieve and maintain normal mitochondrial function. Regarding miRNAs in mitochondria, it is well-recognized nowadays that several cellular mechanisms involving mitochondria are regulated by many genetic players that originate from either nuclear- or mitochondrial-encoded small noncoding RNAs (sncRNAs). Growing evidence collected from whole genome and transcriptome sequencing highlight the role of distinct members of this class, from short interfering RNAs (siRNAs) to miRNAs and long noncoding RNAs (lncRNAs). Some of the mechanisms that have been shown to be modulated are the expression of mitochondrial proteins itself, as well as the more complex coordination of mitochondrial structure and dynamics with its function. We devote particular attention to the role of mitochondrial miRNAs and to their role in the modulation of several molecular processes that could ultimately contribute to tissue regeneration accomplishment.

scholarly journals Role of fluctuations in the yielding transition of two-dimensional glasses

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Misaki Ozawa ◽  
Ludovic Berthier ◽  
Giulio Biroli ◽  
Gilles Tarjus
Keyword(s):  
Two Dimensional
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