NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB-P, and H3K27ac

Fernando J. Bustos, Nur Jury, Pablo Martinez, Estibaliz Ampuero, Matias Campos, Sebastian Abarzúa, Karen Jaramillo, Susanne Ibing, Muriel D. Mardones, Henny Haensgen, Julia Kzhyshkowska, Maria Florencia Tevy, Rachael Neve, Magdalena Sanhueza, Lorena Varela-Nallar, Martín Montecino, Brigitte van Zundert

Resultado de la investigación: Article

9 Citas (Scopus)

Resumen

Dendrite arbor growth, or dendritogenesis, is choreographed by a diverse set of cues, including the NMDA receptor (NMDAR) subunits NR2A and NR2B. While NR1NR2B receptors are predominantly expressed in immature neurons and promote plasticity, NR1NR2A receptors are mainly expressed in mature neurons and induce circuit stability. How the different subunits regulate these processes is unclear, but this is likely related to the presence of their distinct C-terminal sequences that couple different signaling proteins. Calcium-calmodulin-dependent protein kinase II (CaMKII) is an interesting candidate as this protein can be activated by calcium influx through NMDARs. CaMKII triggers a series of biochemical signaling cascades, involving the phosphorylation of diverse targets. Among them, the activation of cAMP response element-binding protein (CREB-P) pathway triggers a plasticity-specific transcriptional program through unknown epigenetic mechanisms. Here, we found that dendritogenesis in hippocampal neurons is impaired by several well-characterized constructs (i.e., NR2B-RS/QD) and peptides (i.e., tatCN21) that specifically interfere with the recruitment and interaction of CaMKII with the NR2B C-terminal domain. Interestingly, we found that transduction of NR2AΔIN, a mutant NR2A construct with increased interaction to CaMKII, reactivates dendritogenesis in mature hippocampal neurons in vitro and in vivo. To gain insights into the signaling and epigenetic mechanisms underlying NMDAR-mediated dendritogenesis, we used immunofluorescence staining to detect CREB-P and acetylated lysine 27 of histone H3 (H3K27ac), an activation-associated histone tail mark. In contrast to control mature neurons, our data shows that activation of the NMDAR/CaMKII/ERK-P/CREB-P signaling axis in neurons expressing NR2AΔIN is not correlated with increased nuclear H3K27ac levels.

Idioma originalEnglish
Páginas (desde-hasta)3677-3692
Número de páginas16
PublicaciónJournal of Cellular Physiology
Volumen232
N.º12
DOI
EstadoPublished - 1 dic 2017

Huella dactilar

Calcium-Calmodulin-Dependent Protein Kinase Type 2
Cyclic AMP Response Element-Binding Protein
N-Methyl-D-Aspartate Receptors
Neurons
Chemical analysis
Chemical activation
Epigenomics
Histones
Plasticity
Histone Code
Calcium-Calmodulin-Dependent Protein Kinases
Phosphorylation
Dendrites
Lysine
Cues
Fluorescent Antibody Technique
Proteins
Staining and Labeling
Calcium
Peptides

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Citar esto

Bustos, Fernando J. ; Jury, Nur ; Martinez, Pablo ; Ampuero, Estibaliz ; Campos, Matias ; Abarzúa, Sebastian ; Jaramillo, Karen ; Ibing, Susanne ; Mardones, Muriel D. ; Haensgen, Henny ; Kzhyshkowska, Julia ; Tevy, Maria Florencia ; Neve, Rachael ; Sanhueza, Magdalena ; Varela-Nallar, Lorena ; Montecino, Martín ; van Zundert, Brigitte. / NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB-P, and H3K27ac. En: Journal of Cellular Physiology. 2017 ; Vol. 232, N.º 12. pp. 3677-3692.
@article{2b54d9cb092347b6aa7b7040a493cd42,
title = "NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB-P, and H3K27ac",
abstract = "Dendrite arbor growth, or dendritogenesis, is choreographed by a diverse set of cues, including the NMDA receptor (NMDAR) subunits NR2A and NR2B. While NR1NR2B receptors are predominantly expressed in immature neurons and promote plasticity, NR1NR2A receptors are mainly expressed in mature neurons and induce circuit stability. How the different subunits regulate these processes is unclear, but this is likely related to the presence of their distinct C-terminal sequences that couple different signaling proteins. Calcium-calmodulin-dependent protein kinase II (CaMKII) is an interesting candidate as this protein can be activated by calcium influx through NMDARs. CaMKII triggers a series of biochemical signaling cascades, involving the phosphorylation of diverse targets. Among them, the activation of cAMP response element-binding protein (CREB-P) pathway triggers a plasticity-specific transcriptional program through unknown epigenetic mechanisms. Here, we found that dendritogenesis in hippocampal neurons is impaired by several well-characterized constructs (i.e., NR2B-RS/QD) and peptides (i.e., tatCN21) that specifically interfere with the recruitment and interaction of CaMKII with the NR2B C-terminal domain. Interestingly, we found that transduction of NR2AΔIN, a mutant NR2A construct with increased interaction to CaMKII, reactivates dendritogenesis in mature hippocampal neurons in vitro and in vivo. To gain insights into the signaling and epigenetic mechanisms underlying NMDAR-mediated dendritogenesis, we used immunofluorescence staining to detect CREB-P and acetylated lysine 27 of histone H3 (H3K27ac), an activation-associated histone tail mark. In contrast to control mature neurons, our data shows that activation of the NMDAR/CaMKII/ERK-P/CREB-P signaling axis in neurons expressing NR2AΔIN is not correlated with increased nuclear H3K27ac levels.",
keywords = "brain, CaMKII, cultures, dendrites, H3K27Ac, histone modification, neuron, NMDAR, spines",
author = "Bustos, {Fernando J.} and Nur Jury and Pablo Martinez and Estibaliz Ampuero and Matias Campos and Sebastian Abarz{\'u}a and Karen Jaramillo and Susanne Ibing and Mardones, {Muriel D.} and Henny Haensgen and Julia Kzhyshkowska and Tevy, {Maria Florencia} and Rachael Neve and Magdalena Sanhueza and Lorena Varela-Nallar and Mart{\'i}n Montecino and {van Zundert}, Brigitte",
year = "2017",
month = "12",
day = "1",
doi = "10.1002/jcp.25843",
language = "English",
volume = "232",
pages = "3677--3692",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "12",

}

Bustos, FJ, Jury, N, Martinez, P, Ampuero, E, Campos, M, Abarzúa, S, Jaramillo, K, Ibing, S, Mardones, MD, Haensgen, H, Kzhyshkowska, J, Tevy, MF, Neve, R, Sanhueza, M, Varela-Nallar, L, Montecino, M & van Zundert, B 2017, 'NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB-P, and H3K27ac', Journal of Cellular Physiology, vol. 232, n.º 12, pp. 3677-3692. https://doi.org/10.1002/jcp.25843

NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB-P, and H3K27ac. / Bustos, Fernando J.; Jury, Nur; Martinez, Pablo; Ampuero, Estibaliz; Campos, Matias; Abarzúa, Sebastian; Jaramillo, Karen; Ibing, Susanne; Mardones, Muriel D.; Haensgen, Henny; Kzhyshkowska, Julia; Tevy, Maria Florencia; Neve, Rachael; Sanhueza, Magdalena; Varela-Nallar, Lorena; Montecino, Martín; van Zundert, Brigitte.

En: Journal of Cellular Physiology, Vol. 232, N.º 12, 01.12.2017, p. 3677-3692.

Resultado de la investigación: Article

TY - JOUR

T1 - NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB-P, and H3K27ac

AU - Bustos, Fernando J.

AU - Jury, Nur

AU - Martinez, Pablo

AU - Ampuero, Estibaliz

AU - Campos, Matias

AU - Abarzúa, Sebastian

AU - Jaramillo, Karen

AU - Ibing, Susanne

AU - Mardones, Muriel D.

AU - Haensgen, Henny

AU - Kzhyshkowska, Julia

AU - Tevy, Maria Florencia

AU - Neve, Rachael

AU - Sanhueza, Magdalena

AU - Varela-Nallar, Lorena

AU - Montecino, Martín

AU - van Zundert, Brigitte

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Dendrite arbor growth, or dendritogenesis, is choreographed by a diverse set of cues, including the NMDA receptor (NMDAR) subunits NR2A and NR2B. While NR1NR2B receptors are predominantly expressed in immature neurons and promote plasticity, NR1NR2A receptors are mainly expressed in mature neurons and induce circuit stability. How the different subunits regulate these processes is unclear, but this is likely related to the presence of their distinct C-terminal sequences that couple different signaling proteins. Calcium-calmodulin-dependent protein kinase II (CaMKII) is an interesting candidate as this protein can be activated by calcium influx through NMDARs. CaMKII triggers a series of biochemical signaling cascades, involving the phosphorylation of diverse targets. Among them, the activation of cAMP response element-binding protein (CREB-P) pathway triggers a plasticity-specific transcriptional program through unknown epigenetic mechanisms. Here, we found that dendritogenesis in hippocampal neurons is impaired by several well-characterized constructs (i.e., NR2B-RS/QD) and peptides (i.e., tatCN21) that specifically interfere with the recruitment and interaction of CaMKII with the NR2B C-terminal domain. Interestingly, we found that transduction of NR2AΔIN, a mutant NR2A construct with increased interaction to CaMKII, reactivates dendritogenesis in mature hippocampal neurons in vitro and in vivo. To gain insights into the signaling and epigenetic mechanisms underlying NMDAR-mediated dendritogenesis, we used immunofluorescence staining to detect CREB-P and acetylated lysine 27 of histone H3 (H3K27ac), an activation-associated histone tail mark. In contrast to control mature neurons, our data shows that activation of the NMDAR/CaMKII/ERK-P/CREB-P signaling axis in neurons expressing NR2AΔIN is not correlated with increased nuclear H3K27ac levels.

AB - Dendrite arbor growth, or dendritogenesis, is choreographed by a diverse set of cues, including the NMDA receptor (NMDAR) subunits NR2A and NR2B. While NR1NR2B receptors are predominantly expressed in immature neurons and promote plasticity, NR1NR2A receptors are mainly expressed in mature neurons and induce circuit stability. How the different subunits regulate these processes is unclear, but this is likely related to the presence of their distinct C-terminal sequences that couple different signaling proteins. Calcium-calmodulin-dependent protein kinase II (CaMKII) is an interesting candidate as this protein can be activated by calcium influx through NMDARs. CaMKII triggers a series of biochemical signaling cascades, involving the phosphorylation of diverse targets. Among them, the activation of cAMP response element-binding protein (CREB-P) pathway triggers a plasticity-specific transcriptional program through unknown epigenetic mechanisms. Here, we found that dendritogenesis in hippocampal neurons is impaired by several well-characterized constructs (i.e., NR2B-RS/QD) and peptides (i.e., tatCN21) that specifically interfere with the recruitment and interaction of CaMKII with the NR2B C-terminal domain. Interestingly, we found that transduction of NR2AΔIN, a mutant NR2A construct with increased interaction to CaMKII, reactivates dendritogenesis in mature hippocampal neurons in vitro and in vivo. To gain insights into the signaling and epigenetic mechanisms underlying NMDAR-mediated dendritogenesis, we used immunofluorescence staining to detect CREB-P and acetylated lysine 27 of histone H3 (H3K27ac), an activation-associated histone tail mark. In contrast to control mature neurons, our data shows that activation of the NMDAR/CaMKII/ERK-P/CREB-P signaling axis in neurons expressing NR2AΔIN is not correlated with increased nuclear H3K27ac levels.

KW - brain

KW - CaMKII

KW - cultures

KW - dendrites

KW - H3K27Ac

KW - histone modification

KW - neuron

KW - NMDAR

KW - spines

UR - http://www.scopus.com/inward/record.url?scp=85018886001&partnerID=8YFLogxK

U2 - 10.1002/jcp.25843

DO - 10.1002/jcp.25843

M3 - Article

VL - 232

SP - 3677

EP - 3692

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 12

ER -