The rate of information transmission through the MAPK/ERKsignaling pathway stimulated in a pulsatile manner

Abstract

Living cells utilize signaling pathways to sense, transduce, and process information. As the extracellular stimulation often has rich temporal characteristics which may govern dynamic cellular responses, it is important to quantify the rate of information flow through the signaling pathways. In this study, we used an epithelial cell line expressing a light-activatable FGF receptor and an ERK activity reporter to assess the ability of the MAPK/ERK pathway to transduce signal encoded in a sequence of pulses. By stimulating the cells with random light pulse trains, we demonstrated that the MAPK/ERK channel capacity is at least 6 bits per hour. The input reconstruction algorithm detects the light pulses with 1-min accuracy 5 min after their occurrence. The high information transmission rate may enable the pathway to coordinate multiple processes including cell movement and respond to rapidly varying stimuli such as chemoattracting gradients created by other cells. Author summaryTo respond to external stimulation, living cells need to transfer information from membrane receptors to downstream proteins that regulate physiological outcomes. In this study we used cells expressing a light-activatable receptor that transmits signals to MAPK/ERK transduction pathway, which regulates numerous physiological processes including proliferation, differentiation and cell motility. By stimulating these cells with various sequences of short light pulses we found that ERK, the last component of the considered signal transduction pathway, may receive at least 6 bits per hour. This bitrate allows 6 binary decisions per hour, enabling rapid responses to varied extracellular stimuli.