The temporal pattern of stimulation determines the extent and duration of MAPK activation in a Caenorhabditis elegans sensory neuron.
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.
1Division of Molecular Cell Signaling, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Taichiro
T
Tomida
Shigekazu
S
Oda
Mutsuhiro
M
Takekawa
Yuichi
Y
Iino
Haruo
H
Saito
D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D007700:Kinetics; D020935:MAP Kinase Signaling System; D008856:Microscopy, Fluorescence / Q000379:methods; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism*; D013997:Time Factors
D029742:Caenorhabditis elegans Proteins; D019950:Mitogen-Activated Protein Kinase 1; C085697:mpk-1 protein, C elegans; D002118:Calcium