Photoactivation of Extracellular‐Signal‐Regulated Kinase Signaling in Target Cells by Femtosecond Laser

Abstract

AbstractOptogenetics employs light to manipulate cellular events such as activation of molecular channels, signaling molecules, and gene transcription, by transfection with engineered light‐sensitive proteins. In the last decade, great progresses in life science have been made by optogenetics, but the gene transfection limits its further medical applications. In this study, it is reported that a short flash of femtosecond‐laser stimulation can directly activate extracellular signal‐regulated kinase (ERK), an essential signaling pathway, in target cells, without any optogenetic technology. This all‐optical approach can be easily accomplished by a two‐photon or confocal microscope coupled with a femtosecond laser. The photostimulation can initiate immediate ERK translocation into nucleus and exit back to cytosol. The nuclear ERK level can be regulated by combination of multiple photostimulations. Subsequent up‐regulation of phosphorylated endogenous eIF4E indicates successful activation of the ERK signaling pathway. Occasionally, ERK activation in the surrounding cells of the stimulation is observed. Some key signaling cascades in the ERK2 pathway activated by photostimulation is further clarified. Altogether, this all‐optical method can activate ERK without any exogenous chemicals or proteins and thus be with promissing potential for related research.