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

Authors: Pérez-Otaño, Isabel  Luján, Rafael  Tavalin, Steven J  Plomann, Markus  Modregger, Jan  Liu, Xiao-Bo  Jones, Edward G  Heinemann, Stephen F  Lo, Donald C  Ehlers, Michael D 
Citation: Pérez-Otaño I, etal., Nat Neurosci. 2006 May;9(5):611-21. doi: 10.1038/nn1680. Epub 2006 Apr 16.
Pubmed: (View Article at PubMed) PMID:16617342
DOI: Full-text: DOI:10.1038/nn1680

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.


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CRRD Object Information
CRRD ID: 13702454
Created: 2018-07-18
Species: All species
Last Modified: 2018-07-18
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.