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PMID: 15385609 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cycling of NMDA receptors during trafficking in neurons before synapse formation.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 24 ·No. 38 ·2004-09-22 ·Pages 8253-64

Washbourne P, Liu XB, Jones EG, McAllister AK

Abstract

The trafficking of glutamate receptors in neurons is of the utmost importance for synapse formation and synaptic plasticity. Recently, we demonstrated that both NMDA and AMPA receptors reside in mobile transport packets that are recruited rapidly and independently to nascent synapses. Here, we show that a large proportion of the glutamate receptor clusters in young cortical neurons are present on the surface of dendrites before synapses are formed and these surface-exposed transport packets are mobile. Exocytosis of glutamate receptors to the dendritic surface occurs via a SNARE [soluble n-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor]-dependent SNAP-23-mediated mechanism. Endocytosis occurs rapidly after surface exposure; >50% of surface-labeled NMDA receptors (NMDARs) are endocytosed within 5 min. NMDARs are transported along microtubules on large tubulovesicular organelles, as indicated by immunoelectron microscopy, and are associated with EEA1 (early endosomal antigen 1) and SAP102 (synapse-associated protein 102), as indicated by immunocytochemistry. Most surprisingly, a large proportion of these transport packets cycle through the dendritic plasma membrane before synapse formation. These results suggest a novel model in which NMDARs cycle with the plasma membrane during pauses of movement along microtubules while trafficking.

MeSH Terms
Animals Cell Membrane/metabolism Cells, Cultured Dendrites/metabolism Endocytosis/physiology Exocytosis/physiology Green Fluorescent Proteins Membrane Proteins/metabolism Mice Microscopy, Immunoelectron Microtubules/metabolism,ultrastructure Models, Neurological Neurons/cytology,metabolism Neuropeptides/metabolism Protein Transport/physiology Rats Receptors, Glutamate/metabolism Receptors, N-Methyl-D-Aspartate/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism SNARE Proteins Synapses/metabolism Transfection Vesicular Transport Proteins/genetics,metabolism
Chemicals
Dlg3 protein, rat Membrane Proteins NR1 NMDA receptor Neuropeptides Receptors, Glutamate Receptors, N-Methyl-D-Aspartate Recombinant Fusion Proteins SNARE Proteins Snap23 protein, rat Vesicular Transport Proteins early endosome antigen 1 enhanced green fluorescent protein Green Fluorescent Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Washbourne Philip
Center for Neuroscience, University of California Davis, Davis, California 95616, USA.
Liu Xiao-Bo
Jones Edward G
McAllister A Kimberley
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.2555-04.2004
Published
2004-09-22
Pages
8253-64
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6729693
Subset
IM
Grants
NCI NIH HHS · P01 CA095616 · United States
NEI NIH HHS · R01 EY013584 · United States
NEI NIH HHS · R01 EY13584 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1523/JNEUROSCI.2555-04.2004 PMC Full Text View journal details
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