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 Dissociation of FAK/p130CAS/c-Src Complex during Mitosis: Role of Mitosis-specific Serine Phosphorylation of FAK

1999 ◽  
Vol 144 (2) ◽  
pp. 315-324 ◽  
Author(s):  
Yoshihiko Yamakita ◽  
Go Totsukawa ◽  
Shigeko Yamashiro ◽  
David Fry ◽  
Xiaoe Zhang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Focal Adhesion ◽  
Focal Adhesions ◽  
Cell Spreading ◽  
Mitotic Cell ◽  
Serine Phosphorylation ◽  
Beta Integrin ◽  
Interphase Cells

At mitosis, focal adhesions disassemble and the signal transduction from focal adhesions is inactivated. We have found that components of focal adhesions including focal adhesion kinase (FAK), paxillin, and p130CAS (CAS) are serine/threonine phosphorylated during mitosis when all three proteins are tyrosine dephosphorylated. Mitosis-specific phosphorylation continues past cytokinesis and is reversed during post-mitotic cell spreading. We have found two significant alterations in FAK-mediated signal transduction during mitosis. First, the association of FAK with CAS or c-Src is greatly inhibited, with levels decreasing to 16 and 13% of the interphase levels, respectively. Second, mitotic FAK shows decreased binding to a peptide mimicking the cytoplasmic domain of beta-integrin when compared with FAK of interphase cells. Mitosis-specific phosphorylation is responsible for the disruption of FAK/CAS binding because dephosphorylation of mitotic FAK in vitro by protein serine/threonine phosphatase 1 restores the ability of FAK to associate with CAS, though not with c-Src. These results suggest that mitosis-specific modification of FAK uncouples signal transduction pathways involving integrin, CAS, and c-Src, and may maintain FAK in an inactive state until post-mitotic spreading.

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 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 Recapitulation of the Function and Role of ROS Generated in Response to Heat Stress in Plants

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 371
Author(s):  
Emily Medina ◽  
Su-Hwa Kim ◽  
Miriam Yun ◽  
Won-Gyu Choi
Keyword(s):  
Heat Stress ◽  
Plant Growth ◽  
Intracellular Signaling ◽  
Oxygen Species ◽  
Natural Ecosystems ◽  
Signaling Molecule ◽  
Signaling Systems ◽  
Cell Compartments ◽  
Tropical Area

In natural ecosystems, plants are constantly exposed to changes in their surroundings as they grow, caused by a lifestyle that requires them to live where their seeds fall. Thus, plants strive to adapt and respond to changes in their exposed environment that change every moment. Heat stress that naturally occurs when plants grow in the summer or a tropical area adversely affects plants’ growth and poses a risk to plant development. When plants are subjected to heat stress, they recognize heat stress and respond using highly complex intracellular signaling systems such as reactive oxygen species (ROS). ROS was previously considered a byproduct that impairs plant growth. However, in recent studies, ROS gained attention for its function as a signaling molecule when plants respond to environmental stresses such as heat stress. In particular, ROS, produced in response to heat stress in various plant cell compartments such as mitochondria and chloroplasts, plays a crucial role as a signaling molecule that promotes plant growth and triggers subsequent downstream reactions. Therefore, this review aims to address the latest research trends and understandings, focusing on the function and role of ROS in responding and adapting plants to heat stress.

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