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PMID: 16617342 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature neuroscience ·Vol. 9 ·No. 5 ·2006-05-00 ·Pages 611-21

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

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.

MeSH Terms
Animals Blotting, Western/methods Cells, Cultured Cloning, Molecular/methods Electrophysiology/methods Embryo, Mammalian Endocytosis/drug effects,physiology Fluorescent Antibody Technique/methods Green Fluorescent Proteins/metabolism Hippocampus/cytology Humans In Situ Hybridization/methods Membrane Glycoproteins/genetics,physiology Microscopy, Immunoelectron/methods Mutation/physiology N-Methylaspartate/pharmacology Neurons/cytology,drug effects Proteoglycans/genetics,physiology Rats Receptors, N-Methyl-D-Aspartate/genetics,metabolism Synapses/drug effects,metabolism,ultrastructure Syndecans Transfection/methods Two-Hybrid System Techniques
Chemicals
Membrane Glycoproteins NR3A NMDA receptor Proteoglycans Receptors, N-Methyl-D-Aspartate Syndecans Green Fluorescent Proteins N-Methylaspartate
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Pérez-Otaño Isabel
Department of Neurobiology, Duke University Medical Center, Box 3209, Durham, North Carolina 27710, USA. [email protected]
Luján Rafael
Tavalin Steven J
Plomann Markus
Modregger Jan
Liu Xiao-Bo
Jones Edward G
Heinemann Stephen F
Lo Donald C
Ehlers Michael D
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Article Info
Journal
Nature neuroscience
Abbr.
Nat Neurosci
ISSN
1097-6256
DOI
10.1038/nn1680
Email
[email protected]
Published
2006-05-00
Epub
2006-00-16
Pages
611-21
Language
English
Region
United States
NLM ID
9809671
PMCID
PMC1892311
Subset
IM
Grants
NINDS NIH HHS · R01 NS28709 · United States
NIMH NIH HHS · MH64748 · United States
NINDS NIH HHS · R01 NS047574 · United States
NIMH NIH HHS · R01 MH064748 · United States
NINDS NIH HHS · R01 NS046661 · United States
NINDS NIH HHS · R01 NS039402 · United States
NINDS NIH HHS · R01 NS028709 · United States
NINDS NIH HHS · NS32742 · United States
NINDS NIH HHS · NS39402 · United States
NINDS NIH HHS · NS46661 · United States
Corrections
CommentIn
PMID: 16639406
External Links
PubMed source DOI: 10.1038/nn1680 PMC Full Text View journal details
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