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

Autor: Magdalena Sanhueza, Karen Jaramillo, Maria Florencia Tevy, Julia Kzhyshkowska, Brigitte van Zundert, Muriel D. Mardones, Sebastian Abarzua, Matias Campos, Susanne Ibing, Rachael L. Neve, Fernando J. Bustos, Henny Haensgen, Nur Jury, Estibaliz Ampuero, Lorena Varela-Nallar, Pablo Martinez, Martin Montecino
Rok vydání: 2017
Předmět:
0301 basic medicine
Physiology
Neurogenesis
Protein subunit
Clinical Biochemistry
Gestational Age
Transfection
CREB
Hippocampus
Receptors
N-Methyl-D-Aspartate
Histones
Rats
Sprague-Dawley
03 medical and health sciences
Histone H3
0302 clinical medicine
Ca2+/calmodulin-dependent protein kinase
medicine
Animals
Protein Interaction Domains and Motifs
Cyclic AMP Response Element-Binding Protein
Receptor
Protein Kinase Inhibitors
Cells
Cultured
Neuronal Plasticity
biology
Chemistry
musculoskeletal
neural
and ocular physiology
Acetylation
Dendrites
Cell Biology
Cell biology
Phenotype
030104 developmental biology
medicine.anatomical_structure
nervous system
Mutation
biology.protein
RNA Interference
Neuron
Signal transduction
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Peptides
Protein Processing
Post-Translational
psychological phenomena and processes
030217 neurology & neurosurgery
Protein Binding
Signal Transduction
Zdroj: Journal of Cellular Physiology
Artículos CONICYT
CONICYT Chile
instacron:CONICYT
J Cell Physiol
ISSN: 0021-9541
Popis: 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.
Databáze: OpenAIRE
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