Unloading of intercellular tension induces the directional translocation of PKCα

The migration of endothelial cells (ECs) is closely associated with a Ca2+-dependent protein, protein kinase C alpha (PKC alpha). The disruption of intercellular adhesion by single-cell wounding has been shown to induce the directional translocation of PKC alpha. We hypothesized that this translocation of PKC alpha is induced by mechanical stress, such as unloading of intercellular tension, or by intercellular communication, such as gap junction-mediated and paracrine signaling. In the current study, we found that the disruption of intercellular adhesion induced the directional translocation of PKC alpha even when gap junction-mediated and paracrine signaling were inhibited. Conversely, it did not occur when the mechanosensitive channel was inhibited. In addition, the strain field of substrate attributable to the disruption of intercellular adhesion tended to be larger at the areas corresponding with PKC alpha translocation. Recently, we found that a direct mechanical stimulus induced the accumulation of PKC alpha at the stimulus area, involving Ca2+ influx from extracellular space. These results indicated that the unloading of intercellular tension induced directional translocation of PKC alpha, which required Ca2+ influx from extracellular space. The results of this study indicate the involvement of PKC alpha in the Ca2+ signaling pathway in response to mechanical stress in ECs.