Biology subjects

De Pascalis, C.

Publications and source records attributed to De Pascalis, C..

3 recordsLinked to original sources

bioRxiv2024

Centrosome positioning independently of microtubule-based forces

The regulation of centrosome position is central to the establishment of polarized cell functions. This process is thought to rely on the generation of mechanical forces along microtubules, the balance of which determines centrosome position. By studying these forces in adherent cells in culture, we found that neither pushing nor pulling forces propagate along microtubules to the centrosome. Inhibiting dyneins or disassembling microtubules did not disrupt the maintenance of the centrosome at the center of the cell. In contrast, the actomyosin contractile network appears to be responsible for the generation of a centripetal flow that drives the centrosome towards the center of the cell independently of the microtubules. Furthermore, we found that centering of the centrosome depends more on the reorganization of cell shape around the centrosome than on an effective centrosome displacement throughout the cytoplasm. Interestingly, despite their lack of mechanical role, microtubules appear to direct this remodeling of cell shape. This revised view of centrosome positioning offers a new perspective for understanding the establishment of cell polarity.

cell biology↗

bioRxiv2020

Microtubules tune mechanosensitive cell responses

Mechanotransduction 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 (TAT1) 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.

cell biology↗

bioRxiv2018

Intermediate filaments control collective migration by restricting traction forces and sustaining cell-cell contacts

Mesenchymal cell migration relies on the coordinated regulation of the actin and microtubule networks which participate in polarised cell protrusion, adhesion and contraction. During collective migration, most of the traction forces are generated by the acto-myosin network linked to focal adhesions at the front of leader cells, which transmit these pulling forces to the followers. Here, using an in vitro wound healing assay to induce polarisation and collective directed migration of primary astrocytes, we show that the intermediate filament (IF) network composed of vimentin, GFAP and nestin contributes to directed collective movement by controlling the distribution of forces in the migrating cell monolayer. Together with the cytoskeletal linker plectin, these IFs control the organisation and dynamics of the acto-myosin network, promoting the actin-driven treadmilling of adherens junctions, thereby facilitating the polarisation of leader cells. Independently of their effect on adherens junctions, IFs influence the dynamics and localisation of focal adhesions and limit their mechanical coupling to the acto-myosin network. We thus conclude that IFs promote collective directed migration by restricting the generation of traction forces to the front of leader cells, preventing aberrant tractions in the followers and by contributing to the maintenance of lateral cell-cell interactions.

cell biology↗