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Biology subjects

Caillier, A.

Publications and source records attributed to Caillier, A..

3 recordsLinked to original sources

Mechanically-induced Septin Networks Protect Nuclear Integrity

The cytoskeleton is a key mediator of mechanical interactions in cells, but specific contributions of septins remains unclear. Septins preferentially localize with a subset of actin stress fibers positioned under the nucleus, where they are situated between the membrane and stress fibers. Removing the nucleus from the cell results in the loss of these subnuclear septin-decorated stress fibers. Surprisingly, however, their formation can be rescued using a large glass bead in place of the nucleus. Similarly, applying a compressive force to the cell via confinement, whether externally or through internally generated actomyosin forces, results in increased septin accumulation in regions where the nucleus engages the cell cortex. Finally, loss of septin filaments via knockdown of SEPT7 increases the likelihood of nuclear membrane rupture during confinement. Together these data suggest that septins act as a dynamic mechanosensitive protective mechanism to buffer mechanical forces on the nucleus.

cell biology↗

T cells Use Focal Adhesions to Pull Themselves Through Confined Environments

Immune cells are highly dynamic and able to migrate through environments with diverse biochemical and mechanical composition. Their migration has classically been defined as amoeboid under the assumption that it is integrin-independent. Here we show that activated primary Th1 T cells require both confinement and extracellular matrix protein to migrate efficiently. This migration is mediated through small and dynamic focal adhesions that are composed of the same proteins associated with canonical mesenchymal focal adhesions, such as integrins, talin, and vinculin. These focal adhesions, furthermore, localize to sites of contractile traction stresses, enabling T cells to pull themselves through confined spaces. Finally, we show that Th1 T cell preferentially follows tracks of other T cells, suggesting that these adhesions are modifying the extracellular matrix to provide additional environmental guidance cues. These results demonstrate not only that the boundaries between amoeboid and mesenchymal migration modes are ambiguous, but that integrin-mediated adhesions play a key role in T cell motility. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=175 SRC="FIGDIR/small/562587v1_ufig1.gif" ALT="Figure 1"> View larger version (78K): org.highwire.dtl.DTLVardef@8ba84aorg.highwire.dtl.DTLVardef@d5a504org.highwire.dtl.DTLVardef@44d104org.highwire.dtl.DTLVardef@1f68df5_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

eIf2α-regulated translation modulates the early adhesion of mesenchymal-like cells

Cellular invasion is a complex process that requires several interdependent biological mechanisms, which are initiated by changes in adhesion that establish a morphology favorable for migration. Hence, the regulation of adhesion potential is a rate-limiting step in metastasis. Our previous work revealed that de novo translation is necessary to regulate the adhesion of mesenchymal-like cells; however, the underlying translational regulatory mechanism and the identity of newly synthesized proteins needed for the adhesion process remain unidentified. Here, we identify a mechanotransduction pathway linking force-mediated protein unfolding to translational reprogramming via the activation of the integrated stress response (ISR). Specifically, we demonstrate that phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2) during early adhesion events leads to selective translation of mRNAs encoding proteins critical for adhesion complex formation, mechanosensing, and contractility. These findings uncover a mechanosensitive translational control axis that links intracellular force generation to cell adhesion and stress adaptation, with implications for understanding mesenchymal cell adhesion and morphological behavior

cell biology↗