Unloading of intercellular tension induces the directional translocation of PKCα.

The migration of endothelial cells (ECs) is closely associated with a Ca -dependent protein, protein kinase Cα (PKCα). The disruption of intercellular adhesion by single-cell wounding has been shown to induce the directional translocation of PKCα. We hypothesized that this translocation of PKCα is induced by mechanical stress, such as unloading of intercellular tension, or by intercellular communication, such as gap junction-mediated and paracrine signaling.

Three-dimensional model of intracellular and intercellular Ca waves propagation in endothelial cells.

Intracellular and intercellular Ca waves play key roles in cellular functions, and focal stimulation triggers Ca wave propagation from stimulation points to neighboring cells, involving localized metabolism reactions and specific diffusion processes. Among these, inositol 1,4,5-trisphosphate (IP) is produced at membranes and diffuses into the cytoplasm to release Ca from endoplasmic reticulum (ER). In this study, we developed a three-dimensional (3D) simulation model for intercellular and intracellular Ca waves in endothelial cells (ECs).

Spatial and temporal translocation of PKCα in single endothelial cell in response to mechanical stimulus.

Endothelial cells (ECs) are exposed to various environmental forces, and a Ca wave is occurred in mechanical stimulated cells. Pharmacological studies reveal that the translocation of protein kinase Cα (PKCα) to the membrane is observed simultaneously with intracellular Ca wave. In this study, we investigate whether and how the kinetics of PKCα in ECs is induced in response to mechanical stress.

Biphasic and directed translocation of protein kinase Cα inside cultured endothelial cells before migration.

Mechanical wounding of an endothelial monolayer induces an immediate Ca wave. Several hours later, the denuded area is covered by endothelial cells (ECs) that migrate to the wound. This migration process is closely related to protein kinase Cα (PKCα), a Ca-dependent protein that translocates from the cytosol to the cell membrane.