PSD95 suppresses dendritic arbor development in mature hippocampal neurons by occluding the clustering of NR2B-NMDA receptors
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Fecha
2014-04
Profesor/a Guía
Facultad/escuela
Idioma
en
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Editor
Public Library of Science
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Licencia CC
Atribution 4.0 International (CC BY 4.0)
Licencia CC
https://creativecommons.org/licenses/by/4.0/deed.es
Resumen
Considerable evidence indicates that the NMDA receptor (NMDAR) subunits NR2A and NR2B are critical mediators of
synaptic plasticity and dendritogenesis; however, how they differentially regulate these processes is unclear. Here we
investigate the roles of the NR2A and NR2B subunits, and of their scaffolding proteins PSD-95 and SAP102, in remodeling
the dendritic architecture of developing hippocampal neurons (2–25 DIV). Analysis of the dendritic architecture and the
temporal and spatial expression patterns of the NMDARs and anchoring proteins in immature cultures revealed a strong
positive correlation between synaptic expression of the NR2B subunit and dendritogenesis. With maturation, the pruning of
dendritic branches was paralleled by a strong reduction in overall and synaptic expression of NR2B, and a significant
elevation in synaptic expression of NR2A and PSD95. Using constructs that alter the synaptic composition, we found that
either over-expression of NR2B or knock-down of PSD95 by shRNA-PSD95 augmented dendritogenesis in immature
neurons. Reactivation of dendritogenesis could also be achieved in mature cultured neurons, but required both
manipulations simultaneously, and was accompanied by increased dendritic clustering of NR2B. Our results indicate that the
developmental increase in synaptic expression of PSD95 obstructs the synaptic clustering of NR2B-NMDARs, and thereby
restricts reactivation of dendritic branching. Experiments with shRNA-PSD95 and chimeric NR2A/NR2B constructs further
revealed that C-terminus of the NR2B subunit (tail) was sufficient to induce robust dendritic branching in mature
hippocampal neurons, and suggest that the NR2B tail is important in recruiting calcium-dependent signaling proteins and
scaffolding proteins necessary for dendritogenesis.
Notas
Indexación Scopus.
Palabras clave
Neuronal Dendrites, Hippocampus, Neurons, Transfection, Developmental Neuroscience, Spinal Cord, Dendritic Structure, Synapses
Citación
PLoS ONE. Volume 9, Issue 4. 4 April 2014. Article number e94037
DOI
DOI: 10.1371/journal.pone.0094037