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


Journal Article

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.

Full Text

Cited Authors

  • Pérez-Otaño, I; Luján, R; Tavalin, SJ; Plomann, M; Modregger, J; Liu, X-B; Jones, EG; Heinemann, SF; Lo, DC; Ehlers, MD

Published Date

  • May 2006

Published In

Volume / Issue

  • 9 / 5

Start / End Page

  • 611 - 621

PubMed ID

  • 16617342

Pubmed Central ID

  • 16617342

Electronic International Standard Serial Number (EISSN)

  • 1546-1726

International Standard Serial Number (ISSN)

  • 1097-6256

Digital Object Identifier (DOI)

  • 10.1038/nn1680


  • eng