Light-Controlled Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Live Cells

Abstract

The Mitogen-Activated Protein Kinase (MAPK) signaling pathway regulates critical cellular function such as cell proliferation, differentiation, and apoptosis. Defective MAPK signaling has been frequently discovered in various cancers such as in breast cancer, lung cancer, and melanoma. Evidence showed that signaling output of the MAPK pathway depends critically on its spatiotemporal regulation. However, there are very limited means to control its spatial and temporal dimension in live cells with high accuracy. Here, we report a light-gated protein-protein interaction system that precisely regulates the activation and inactivation of the MAPK signaling pathway. We show that sustained MAPK activation through continuous light stimulation is sufficient to induce significant neurite outgrowth in PC12 cells in the absence of nerve growth factor. Light-gated activation leads to an interesting discovery that MAPK alone is sufficient to account for neurite elongation, it only partially contributes to the full development of sodium channels in PC12 cells. The strategy of using light-gated protein interaction shows a great promise in dissecting detailed mechanisms of signal transduction in cells.