Microtubules tune mechanosensitive cell responses

AbstractMechanotransduction is a process by which cells sense the mechanical properties of their surrounding environment and adapt accordingly to perform cellular functions such as adhesion, migration and differentiation. Integrin-mediated focal adhesions are major sites of mechanotransduction and their connection with the actomyosin network is crucial for mechanosensing as well as the generation and transmission of forces onto the substrate. Despite having emerged as major regulators of cell adhesion and migration, the contribution of microtubules to mechanotransduction still remains elusive. Here, we show that actomyosin-dependent mechanosensing of substrate rigidity controls microtubule acetylation, a tubulin post-translational modification, by promoting the recruitment of the alpha-tubulin acetyl transferase (αTAT1) to focal adhesions. Microtubule acetylation, in turn, promotes GEF-H1 mediated RhoA activation, actomyosin contractility and traction forces. Our results reveal a fundamental crosstalk between microtubules and actin in mechanotransduction, which contributes to mechanosensitive cell adhesion and migration.

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The Role of Lipid Rafts in Cancer Cell Adhesion and Migration

International Journal of Cell Biology ◽

10.1155/2012/763283 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 51

Author(s):

Toshiyuki Murai

Keyword(s):

Cell Adhesion ◽

Lipid Rafts ◽

Cancer Cell ◽

Cancer Progression ◽

Migration And Invasion ◽

Dynamic Features ◽

Cellular Functions ◽

Cancer Cell Adhesion ◽

Cell Adhesion And Migration ◽

And Migration

Lipid rafts are cholesterol-enriched microdomains of the cell membrane and possess a highly dynamic nature. They have been involved in various cellular functions including the regulation of cell adhesion and membrane signaling through proteins within lipid rafts. The dynamic features of the cancer cell surface may modulate the malignant phenotype of cancer, including adhesion disorders and aggressive phenotypes of migration and invasion. Recently, it was demonstrated that lipid rafts play critical roles in cancer cell adhesion and migration. This article summarizes the important roles of lipid rafts in cancer cell adhesion and migration, with a focus on the current state of knowledge. This article will improve the understanding of cancer progression and lead to the development of novel targets for cancer therapy.

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PAK4 methylation by the methyltransferase SETD6 attenuates cell adhesion

Scientific Reports ◽

10.1038/s41598-020-74081-1 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Zlata Vershinin ◽

Michal Feldman ◽

Dan Levy

Keyword(s):

Cell Adhesion ◽

Mammalian Cells ◽

Focal Adhesions ◽

Vital Role ◽

Migration And Invasion ◽

Wild Type ◽

Set Domain ◽

Cell Adhesion And Migration ◽

P21 Activated Kinase ◽

And Migration

Abstract P21-activated kinase 4 (PAK4), a member of serine/threonine kinases family is over-expressed in numerous cancer tumors and is associated with oncogenic cell proliferation, migration and invasion. Our recent work demonstrated that the SET-domain containing protein 6 (SETD6) interacts with and methylates PAK4 at chromatin in mammalian cells, leading to activation of the Wnt/β-catenin signaling pathway. In our current work, we identified lysine 473 (K473) on PAK4 as the primary methylation site by SETD6. Methylation of PAK4 at K473 activates β-catenin transcriptional activity and inhibits cell adhesion. Specific methylation of PAK4 at K473 also attenuates paxillin localization to focal adhesions leading to overall reduction in adhesion-related features, such as filopodia and actin structures. The altered adhesion of the PAK4 wild-type cells is accompanied with a decrease in the migrative and invasive characteristics of the cells. Taken together, our results suggest that methylation of PAK4 at K473 plays a vital role in the regulation of cell adhesion and migration.

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Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration

Scientific Reports ◽

10.1038/srep18476 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 28

Author(s):

Jui-Chung Wu ◽

Yu-Chen Chen ◽

Chih-Ting Kuo ◽

Helen Wenshin Yu ◽

Yin-Quan Chen ◽

...

Keyword(s):

Cell Adhesion ◽

Focal Adhesion Kinase ◽

Focal Adhesion ◽

Focal Adhesions ◽

Sh2 Domains ◽

Cell Adhesion And Migration ◽

And Migration

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Ubiquitin links to cytoskeletal dynamics, cell adhesion and migration

Biochemical Journal ◽

10.1042/bj20111815 ◽

2012 ◽

Vol 442 (1) ◽

pp. 13-25 ◽

Cited By ~ 30

Author(s):

Antje Schaefer ◽

Micha Nethe ◽

Peter L. Hordijk

Keyword(s):

Cell Adhesion ◽

Protein Interactions ◽

Protein Modification ◽

Covalent Attachment ◽

Cellular Functions ◽

Vesicular Traffic ◽

Additional Information ◽

Cytoskeletal Dynamics ◽

Cell Adhesion And Migration ◽

And Migration

Post-translational modifications are used by cells to link additional information to proteins. Most modifications are subtle and concern small moieties such as a phosphate group or a lipid. In contrast, protein ubiquitylation entails the covalent attachment of a full-length protein such as ubiquitin. The protein ubiquitylation machinery is remarkably complex, comprising more than 15 Ubls (ubiquitin-like proteins) and several hundreds of ubiquitin-conjugating enzymes. Ubiquitin is best known for its role as a tag that induces protein destruction either by the proteasome or through targeting to lysosomes. However, addition of one or more Ubls also affects vesicular traffic, protein–protein interactions and signal transduction. It is by now well established that ubiquitylation is a component of most, if not all, cellular signalling pathways. Owing to its abundance in controlling cellular functions, ubiquitylation is also of key relevance to human pathologies, including cancer and inflammation. In the present review, we focus on its role in the control of cell adhesion, polarity and directional migration. It will become clear that protein modification by Ubls occurs at every level from the receptors at the plasma membrane down to cytoskeletal components such as actin, with differential consequences for the pathway's final output. Since ubiquitylation is fast as well as reversible, it represents a bona fide signalling event, which is used to fine-tune a cell's responses to receptor agonists.

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