Endocytosis and synaptic removal of NR3A-containing NMDA receptors by PACSIN1/syndapin1

Isabel Pérez-Otaño, Rafael Luján, Steven Tavalin, Markus Plomann, Jan Modregger, Xiao Bo Liu, Edward G. Jones, Stephen F. Heinemann, Donald C. Lo, Michael D. Ehlers

Research output: Contribution to journalArticle

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Abstract

A key step in glutamatergic synapse maturation is the replacement of developmentally expressed N-methyl-D-aspartate receptors (NMDARs) with mature forms that differ in subunit composition, electrophysiological properties and propensity to elicit synaptic plasticity. However, the mechanisms underlying the removal and replacement of synaptic NMDARs are poorly understood. Here we demonstrate that NMDARs containing the developmentally regulated NR3A subunit undergo rapid endocytosis from the dendritic plasma membrane in cultured rat hippocampal neurons. This endocytic removal is regulated by PACSIN1/syndapin1, which directly and selectively binds the carboxy-terminal domain of NR3A through its NPF motifs and assembles a complex of proteins including dynamin and clathrin. Endocytosis of NR3A by PACSIN1 is activity dependent, and disruption of PACSIN1 function causes NR3A accumulation at synaptic sites. Our results reveal a new activity-dependent mechanism involved in the regulation of NMDAR expression at synapses during development, and identify a brain-specific endocytic adaptor that confers spatiotemporal and subunit specificity to NMDAR endocytosis.

Original languageEnglish (US)
Pages (from-to)611-621
Number of pages11
JournalNature Neuroscience
Volume9
Issue number5
DOIs
StatePublished - May 1 2006

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Endocytosis
N-Methyl-D-Aspartate Receptors
Synapses
Dynamins
Clathrin
Neuronal Plasticity
Cell Membrane
NR3A NMDA receptor
Neurons
Brain
Proteins

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Pérez-Otaño, I., Luján, R., Tavalin, S., Plomann, M., Modregger, J., Liu, X. B., ... Ehlers, M. D. (2006). Endocytosis and synaptic removal of NR3A-containing NMDA receptors by PACSIN1/syndapin1. Nature Neuroscience, 9(5), 611-621. https://doi.org/10.1038/nn1680

Endocytosis and synaptic removal of NR3A-containing NMDA receptors by PACSIN1/syndapin1. / Pérez-Otaño, Isabel; Luján, Rafael; Tavalin, Steven; Plomann, Markus; Modregger, Jan; Liu, Xiao Bo; Jones, Edward G.; Heinemann, Stephen F.; Lo, Donald C.; Ehlers, Michael D.

In: Nature Neuroscience, Vol. 9, No. 5, 01.05.2006, p. 611-621.

Research output: Contribution to journalArticle

Pérez-Otaño, I, Luján, R, Tavalin, S, Plomann, M, Modregger, J, Liu, XB, Jones, EG, Heinemann, SF, Lo, DC & Ehlers, MD 2006, 'Endocytosis and synaptic removal of NR3A-containing NMDA receptors by PACSIN1/syndapin1', Nature Neuroscience, vol. 9, no. 5, pp. 611-621. https://doi.org/10.1038/nn1680
Pérez-Otaño, Isabel ; Luján, Rafael ; Tavalin, Steven ; Plomann, Markus ; Modregger, Jan ; Liu, Xiao Bo ; Jones, Edward G. ; Heinemann, Stephen F. ; Lo, Donald C. ; Ehlers, Michael D. / Endocytosis and synaptic removal of NR3A-containing NMDA receptors by PACSIN1/syndapin1. In: Nature Neuroscience. 2006 ; Vol. 9, No. 5. pp. 611-621.
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