Title:
Role of Myo19, an actin-based mitochondria motor, during collective cell migration.
Abstract:
Cellular migration is essential for embryonic development, wound healing, immune defense, and angiogenesis, but it also is an enhancer of cancer metastasis and inflammation. Cell migration is described as cycles of continuous actin branching at the cell leading edge, focal adhesion (FA) sites assembly, and disassembly and contraction of the cell trailing end. These highly energy-consuming processes require positioning the mitochondria at FA sites and the leading edge of cells to supply ATP. In eukaryotes, mitochondria are solely associated with actin and microtubule filaments. The actin-based transport of mitochondria is mainly by the molecular motor Myo19, which has been shown to transport mitochondria to actin protrusions at the cell’s leading edge during cellular stress. We hypothesize that Myo19 plays an essential role in the motility and positioning of mitochondria in the cell’s leading edge during migration. My goal is to determine the contribution of Myo19 during cellular migration. I will generate stable cell lines of inducible KD of Myo19 and perform collective in vitro cell migration by automated high throughput scratch assay (‘wound healing’) on stable Myo19 KD cells. To this end, the results display a significant reduction in cell migration rates in several cell lines. This suggests that Myo19 plays a role in coupling mitochondria positioning and mobility during cellular migration. Further research on the regulation of Myo19 might provide a new approach to metastatic cancer therapy.
