Synaptic activity induces dramatic changes in the geometry of the cell nucleus: interplay between nuclear structure, histone H3 phosphorylation, and nuclear calcium signaling.
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Synaptic activity induces dramatic changes in the geometry of the cell nucleus: interplay between nuclear structure, histone H3 phosphorylation, and nuclear calcium signaling. / Wittmann, Malte; Queisser, Gillian; Eder, Anja; Wiegert, J. Simon; Bengtson, C Peter; Hellwig, Andrea; Wittum, Gabriel; Bading, Hilmar.
In: J NEUROSCI, Vol. 29, No. 47, 47, 2009, p. 14687-14700.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Synaptic activity induces dramatic changes in the geometry of the cell nucleus: interplay between nuclear structure, histone H3 phosphorylation, and nuclear calcium signaling.
AU - Wittmann, Malte
AU - Queisser, Gillian
AU - Eder, Anja
AU - Wiegert, J. Simon
AU - Bengtson, C Peter
AU - Hellwig, Andrea
AU - Wittum, Gabriel
AU - Bading, Hilmar
PY - 2009
Y1 - 2009
N2 - Synaptic activity initiates many adaptive responses in neurons. Here we report a novel form of structural plasticity in dissociated hippocampal cultures and slice preparations. Using a recently developed algorithm for three-dimensional image reconstruction and quantitative measurements of cell organelles, we found that many nuclei from hippocampal neurons are highly infolded and form unequally sized nuclear compartments. Nuclear infoldings are dynamic structures, which can radically transform the geometry of the nucleus in response to neuronal activity. Action potential bursting causing synaptic NMDA receptor activation dramatically increases the number of infolded nuclei via a process that requires the ERK-MAP kinase pathway and new protein synthesis. In contrast, death-signaling pathways triggered by extrasynaptic NMDA receptors cause a rapid loss of nuclear infoldings. Compared with near-spherical nuclei, infolded nuclei have a larger surface and increased nuclear pore complex immunoreactivity. Nuclear calcium signals evoked by cytosolic calcium transients are larger in small nuclear compartments than in the large compartments of the same nucleus; moreover, small compartments are more efficient in temporally resolving calcium signals induced by trains of action potentials in the theta frequency range (5 Hz). Synaptic activity-induced phosphorylation of histone H3 on serine 10 was more robust in neurons with infolded nuclei compared with neurons with near-spherical nuclei, suggesting a functional link between nuclear geometry and transcriptional regulation. The translation of synaptic activity-induced signaling events into changes in nuclear geometry facilitates the relay of calcium signals to the nucleus, may lead to the formation of nuclear signaling microdomains, and could enhance signal-regulated transcription.
AB - Synaptic activity initiates many adaptive responses in neurons. Here we report a novel form of structural plasticity in dissociated hippocampal cultures and slice preparations. Using a recently developed algorithm for three-dimensional image reconstruction and quantitative measurements of cell organelles, we found that many nuclei from hippocampal neurons are highly infolded and form unequally sized nuclear compartments. Nuclear infoldings are dynamic structures, which can radically transform the geometry of the nucleus in response to neuronal activity. Action potential bursting causing synaptic NMDA receptor activation dramatically increases the number of infolded nuclei via a process that requires the ERK-MAP kinase pathway and new protein synthesis. In contrast, death-signaling pathways triggered by extrasynaptic NMDA receptors cause a rapid loss of nuclear infoldings. Compared with near-spherical nuclei, infolded nuclei have a larger surface and increased nuclear pore complex immunoreactivity. Nuclear calcium signals evoked by cytosolic calcium transients are larger in small nuclear compartments than in the large compartments of the same nucleus; moreover, small compartments are more efficient in temporally resolving calcium signals induced by trains of action potentials in the theta frequency range (5 Hz). Synaptic activity-induced phosphorylation of histone H3 on serine 10 was more robust in neurons with infolded nuclei compared with neurons with near-spherical nuclei, suggesting a functional link between nuclear geometry and transcriptional regulation. The translation of synaptic activity-induced signaling events into changes in nuclear geometry facilitates the relay of calcium signals to the nucleus, may lead to the formation of nuclear signaling microdomains, and could enhance signal-regulated transcription.
KW - Animals
KW - Cells, Cultured
KW - Rats
KW - Rats, Sprague-Dawley
KW - Phosphorylation
KW - Animals, Newborn
KW - Organ Culture Techniques
KW - Action Potentials/physiology
KW - Synaptic Transmission/physiology
KW - Receptors, N-Methyl-D-Aspartate/metabolism
KW - Nuclear Pore/metabolism
KW - Apoptosis/physiology
KW - Calcium Signaling/physiology
KW - Cell Shape/physiology
KW - Histones/metabolism
KW - Cytosol/metabolism
KW - Cell Compartmentation/physiology
KW - Cell Nucleus/metabolism/ultrastructure
KW - Hippocampus/metabolism/ultrastructure
KW - MAP Kinase Signaling System/physiology
KW - Neurons/metabolism/ultrastructure
KW - Nuclear Envelope/metabolism/ultrastructure
KW - Serine/metabolism
KW - Animals
KW - Cells, Cultured
KW - Rats
KW - Rats, Sprague-Dawley
KW - Phosphorylation
KW - Animals, Newborn
KW - Organ Culture Techniques
KW - Action Potentials/physiology
KW - Synaptic Transmission/physiology
KW - Receptors, N-Methyl-D-Aspartate/metabolism
KW - Nuclear Pore/metabolism
KW - Apoptosis/physiology
KW - Calcium Signaling/physiology
KW - Cell Shape/physiology
KW - Histones/metabolism
KW - Cytosol/metabolism
KW - Cell Compartmentation/physiology
KW - Cell Nucleus/metabolism/ultrastructure
KW - Hippocampus/metabolism/ultrastructure
KW - MAP Kinase Signaling System/physiology
KW - Neurons/metabolism/ultrastructure
KW - Nuclear Envelope/metabolism/ultrastructure
KW - Serine/metabolism
M3 - SCORING: Journal article
VL - 29
SP - 14687
EP - 14700
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 47
M1 - 47
ER -