Diffusion and not active transport underlies and limits ERK1/2 synapse-to-nucleus signaling in hippocampal neurons.
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Diffusion and not active transport underlies and limits ERK1/2 synapse-to-nucleus signaling in hippocampal neurons. / Wiegert, J. Simon; Bengtson, C Peter; Bading, Hilmar.
In: J BIOL CHEM, Vol. 282, No. 40, 40, 2007, p. 29621-29633.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Diffusion and not active transport underlies and limits ERK1/2 synapse-to-nucleus signaling in hippocampal neurons.
AU - Wiegert, J. Simon
AU - Bengtson, C Peter
AU - Bading, Hilmar
PY - 2007
Y1 - 2007
N2 - The propagation of signals from synapses and dendrites to the nucleus is crucial for long lasting adaptive changes in the nervous system. The ERK-MAPK pathway can link neuronal activity and cell surface receptor activation to the regulation of gene transcription, and it is often considered the principal mediator of synapse-to-nucleus communication in late-phase plasticity and learning. However, the mechanisms underlying ERK1/2 trafficking in dendrites and nuclear translocation in neurons remain to be determined leaving it unclear whether ERK1/2 activated at the synapse can contribute to nuclear signaling and transcriptional regulation. Using the photobleachable and photoactivable fluorescent tag Dronpa on ERK1 and ERK2, we show here that ERK1/2 translocation to the nucleus of hippocampal neurons is induced by the stimulation of N-methyl-D-aspartate receptors or TrkB stimulation and is apparently mediated by facilitated diffusion. In contrast, ERK1/2 trafficking within dendrites is not signal-regulated and is mediated by passive diffusion. Within dendrites, the reach of a locally activated pool of ERK1/2 is very limited and follows an exponential decay with distance. These results indicate that successful signal propagation to the nucleus by the ERK-MAPK pathway depends on the distance of the nucleus from the site of ERK1/2 activation. ERK1/2 activated within or near the soma may rapidly reach the nucleus to induce gene expression, whereas ERK1/2 activated at distal synapses may only contribute to local signaling.
AB - The propagation of signals from synapses and dendrites to the nucleus is crucial for long lasting adaptive changes in the nervous system. The ERK-MAPK pathway can link neuronal activity and cell surface receptor activation to the regulation of gene transcription, and it is often considered the principal mediator of synapse-to-nucleus communication in late-phase plasticity and learning. However, the mechanisms underlying ERK1/2 trafficking in dendrites and nuclear translocation in neurons remain to be determined leaving it unclear whether ERK1/2 activated at the synapse can contribute to nuclear signaling and transcriptional regulation. Using the photobleachable and photoactivable fluorescent tag Dronpa on ERK1 and ERK2, we show here that ERK1/2 translocation to the nucleus of hippocampal neurons is induced by the stimulation of N-methyl-D-aspartate receptors or TrkB stimulation and is apparently mediated by facilitated diffusion. In contrast, ERK1/2 trafficking within dendrites is not signal-regulated and is mediated by passive diffusion. Within dendrites, the reach of a locally activated pool of ERK1/2 is very limited and follows an exponential decay with distance. These results indicate that successful signal propagation to the nucleus by the ERK-MAPK pathway depends on the distance of the nucleus from the site of ERK1/2 activation. ERK1/2 activated within or near the soma may rapidly reach the nucleus to induce gene expression, whereas ERK1/2 activated at distal synapses may only contribute to local signaling.
KW - Animals
KW - Rats
KW - Rats, Sprague-Dawley
KW - MAP Kinase Signaling System
KW - Biological Transport
KW - Neurons/metabolism
KW - Synapses/metabolism
KW - Active Transport, Cell Nucleus
KW - Diffusion
KW - Cell Nucleus/metabolism
KW - Biological Transport, Active
KW - Hippocampus/metabolism
KW - Mitogen-Activated Protein Kinase 1/metabolism
KW - Mitogen-Activated Protein Kinase 3/metabolism
KW - Rats, Long-Evans
KW - Animals
KW - Rats
KW - Rats, Sprague-Dawley
KW - MAP Kinase Signaling System
KW - Biological Transport
KW - Neurons/metabolism
KW - Synapses/metabolism
KW - Active Transport, Cell Nucleus
KW - Diffusion
KW - Cell Nucleus/metabolism
KW - Biological Transport, Active
KW - Hippocampus/metabolism
KW - Mitogen-Activated Protein Kinase 1/metabolism
KW - Mitogen-Activated Protein Kinase 3/metabolism
KW - Rats, Long-Evans
M3 - SCORING: Journal article
VL - 282
SP - 29621
EP - 29633
JO - J BIOL CHEM
JF - J BIOL CHEM
SN - 0021-9258
IS - 40
M1 - 40
ER -
