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The temporal pattern of stimulation determines the extent and duration of MAPK activation in a Caenorhabditis elegans sensory neuron

Sci Signal. 2012 Oct 16;5(246):ra76. doi: 10.1126/scisignal.2002983.
Tomida T, Oda S, Takekawa M, Iino Y, Saito H.
1Division of Molecular Cell Signaling, Institute of Medical Science, University of Tokyo

The Caenorhabditis elegans ASER sensory neuron is excited when environmental NaCl concentration is decreased. The mitogen-activated protein kinase (MAPK) MPK-1, a homolog of ERK (extracellular signal-regulated kinase), is activated during excitation of ASER sensory neurons. We created and expressed a fluorescence resonance energy transfer (FRET)-based MAPK activity probe in ASER neurons and then exposed the worms to various cyclic patterns of stimulation (changes in NaCl concentration) to monitor the dynamics of MPK-1 activity. We found that the intensity and duration of MPK-1 activity were determined by the temporal pattern of stimulation, namely, a combination of stimulation period length, stimulation duration, and time between stimuli. The complex, nonlinear relationship between stimulation and MPK-1 activation was explained by the properties of intracellular calcium responses upstream of MPK-1. Thus, we visualized the dynamics of MAPK activation in a sensory neuron in living nematodes in response to complex stimuli and present a reporter that can be used in higher eukaryotes to test in silico predictions regarding the MAPK pathway.