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J Neurosci
2004 Aug 11;2432:7096-109. doi: 10.1523/JNEUROSCI.0780-04.2004.
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Endocytosis and degradative sorting of NMDA receptors by conserved membrane-proximal signals.
Scott DB
,
Michailidis I
,
Mu Y
,
Logothetis D
,
Ehlers MD
.
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Regulation of the abundance of NMDA receptors (NMDARs) at excitatory synapses is critical during changes in synaptic efficacy underlying learning and memory as well as during synapse formation throughout neural development. However, the molecular signals that govern NMDAR delivery, maintenance, and internalization remain unclear. In this study, we identify a conserved family of membrane-proximal endocytic signals, two within the NMDAR type 1 (NR1) subunit and one within the NR2A and NR2B subunits, necessary and sufficient to drive the internalization of NMDARs. These endocytic motifs reside in the region of NMDAR subunits immediately after the fourth membrane segment, a region implicated in use-dependent rundown and NMDA channel inactivation. Although endocytosis driven by the distal C-terminal domain of NR2B is followed by rapid recycling, internalization mediated by membrane-proximal motifs selectively targets receptors to late endosomes and accelerates degradation. These results define a novel conserved signature of NMDARs regulating internalization and postendocytic trafficking.
Abraham,
Metaplasticity: the plasticity of synaptic plasticity.
1996, Pubmed
Abraham,
Metaplasticity: the plasticity of synaptic plasticity.
1996,
Pubmed
Barria,
Subunit-specific NMDA receptor trafficking to synapses.
2002,
Pubmed
Bayer,
Interaction with the NMDA receptor locks CaMKII in an active conformation.
2001,
Pubmed
Beattie,
Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD.
2000,
Pubmed
Bolshakov,
Postsynaptic induction and presynaptic expression of hippocampal long-term depression.
1994,
Pubmed
Bonifacino,
Signals for sorting of transmembrane proteins to endosomes and lysosomes.
2003,
Pubmed
Bredt,
AMPA receptor trafficking at excitatory synapses.
2003,
Pubmed
Bresler,
Postsynaptic density assembly is fundamentally different from presynaptic active zone assembly.
2004,
Pubmed
Bucci,
Rab7: a key to lysosome biogenesis.
2000,
Pubmed
Cao,
A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor.
1999,
Pubmed
Carroll,
Role of AMPA receptor endocytosis in synaptic plasticity.
2001,
Pubmed
Carroll,
NMDA-receptor trafficking and targeting: implications for synaptic transmission and plasticity.
2002,
Pubmed
Chavrier,
Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments.
1990,
Pubmed
Ehlers,
Reinsertion or degradation of AMPA receptors determined by activity-dependent endocytic sorting.
2000,
Pubmed
Ehlers,
Inactivation of NMDA receptors by direct interaction of calmodulin with the NR1 subunit.
1996,
Pubmed
Friedman,
Assembly of new individual excitatory synapses: time course and temporal order of synaptic molecule recruitment.
2000,
Pubmed
Goda,
Mechanisms of synapse assembly and disassembly.
2003,
Pubmed
Grosshans,
LTP leads to rapid surface expression of NMDA but not AMPA receptors in adult rat CA1.
2002,
Pubmed
Heynen,
Bidirectional, activity-dependent regulation of glutamate receptors in the adult hippocampus in vivo.
2000,
Pubmed
Hicke,
Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins.
2003,
Pubmed
Kneussel,
Dynamic regulation of GABA(A) receptors at synaptic sites.
2002,
Pubmed
Krapivinsky,
The NMDA receptor is coupled to the ERK pathway by a direct interaction between NR2B and RasGRF1.
2003,
Pubmed
Krupp,
Interactions of calmodulin and alpha-actinin with the NR1 subunit modulate Ca2+-dependent inactivation of NMDA receptors.
1999,
Pubmed
Köhr,
Intracellular domains of NMDA receptor subtypes are determinants for long-term potentiation induction.
2003,
Pubmed
Lavezzari,
Differential binding of the AP-2 adaptor complex and PSD-95 to the C-terminus of the NMDA receptor subunit NR2B regulates surface expression.
2003,
Pubmed
Lee,
Clathrin adaptor AP2 and NSF interact with overlapping sites of GluR2 and play distinct roles in AMPA receptor trafficking and hippocampal LTD.
2002,
Pubmed
Legendre,
Inactivation of NMDA channels in cultured hippocampal neurons by intracellular calcium.
1993,
Pubmed
Leonard,
Regulation of calcium/calmodulin-dependent protein kinase II docking to N-methyl-D-aspartate receptors by calcium/calmodulin and alpha-actinin.
2002,
Pubmed
Li,
Differential regulation of synaptic and extra-synaptic NMDA receptors.
2002,
Pubmed
Liao,
Regulation of morphological postsynaptic silent synapses in developing hippocampal neurons.
1999,
Pubmed
Lin,
Distinct molecular mechanisms and divergent endocytotic pathways of AMPA receptor internalization.
2000,
Pubmed
Malinow,
AMPA receptor trafficking and synaptic plasticity.
2002,
Pubmed
Maxfield,
Endocytic recycling.
2004,
Pubmed
McIlhinney,
Assembly intracellular targeting and cell surface expression of the human N-methyl-D-aspartate receptor subunits NR1a and NR2A in transfected cells.
1998,
Pubmed
Mellman,
Endocytosis and molecular sorting.
1996,
Pubmed
Montgomery,
State-dependent heterogeneity in synaptic depression between pyramidal cell pairs.
2002,
Pubmed
Mori,
Role of the carboxy-terminal region of the GluR epsilon2 subunit in synaptic localization of the NMDA receptor channel.
1998,
Pubmed
Mu,
Activity-dependent mRNA splicing controls ER export and synaptic delivery of NMDA receptors.
2003,
Pubmed
Mukherjee,
Endocytosis.
1997,
Pubmed
Méresse,
The rab7 GTPase resides on a vesicular compartment connected to lysosomes.
1995,
Pubmed
Nong,
Glycine binding primes NMDA receptor internalization.
2003,
Pubmed
Okabe,
Alternative splicing of the C-terminal domain regulates cell surface expression of the NMDA receptor NR1 subunit.
1999,
Pubmed
Oliet,
Two distinct forms of long-term depression coexist in CA1 hippocampal pyramidal cells.
1997,
Pubmed
Philpot,
Visual experience and deprivation bidirectionally modify the composition and function of NMDA receptors in visual cortex.
2001,
Pubmed
Philpot,
Evidence for altered NMDA receptor function as a basis for metaplasticity in visual cortex.
2003,
Pubmed
Prybylowski,
Relationship between availability of NMDA receptor subunits and their expression at the synapse.
2002,
Pubmed
Quinlan,
Rapid, experience-dependent expression of synaptic NMDA receptors in visual cortex in vivo.
1999,
Pubmed
Rao,
Activity regulates the synaptic localization of the NMDA receptor in hippocampal neurons.
1997,
Pubmed
Roche,
Molecular determinants of NMDA receptor internalization.
2001,
Pubmed
Rosenmund,
Calcium-induced actin depolymerization reduces NMDA channel activity.
1993,
Pubmed
Rosenmund,
Rundown of N-methyl-D-aspartate channels during whole-cell recording in rat hippocampal neurons: role of Ca2+ and ATP.
1993,
Pubmed
Scott,
An NMDA receptor ER retention signal regulated by phosphorylation and alternative splicing.
2001,
Pubmed
Scott,
Coordinated PKA and PKC phosphorylation suppresses RXR-mediated ER retention and regulates the surface delivery of NMDA receptors.
2003,
Pubmed
Snyder,
Internalization of ionotropic glutamate receptors in response to mGluR activation.
2001,
Pubmed
Sprengel,
Importance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo.
1998,
Pubmed
Standley,
PDZ domain suppression of an ER retention signal in NMDA receptor NR1 splice variants.
2000,
Pubmed
Steigerwald,
C-Terminal truncation of NR2A subunits impairs synaptic but not extrasynaptic localization of NMDA receptors.
2000,
Pubmed
Sönnichsen,
Distinct membrane domains on endosomes in the recycling pathway visualized by multicolor imaging of Rab4, Rab5, and Rab11.
2000,
Pubmed
Tan,
A leucine-based motif mediates the endocytosis of vesicular monoamine and acetylcholine transporters.
1998,
Pubmed
Tjelle,
Isolation and characterization of early endosomes, late endosomes and terminal lysosomes: their role in protein degradation.
1996,
Pubmed
Turrigiano,
Activity-dependent scaling of quantal amplitude in neocortical neurons.
1998,
Pubmed
Vissel,
A use-dependent tyrosine dephosphorylation of NMDA receptors is independent of ion flux.
2001,
Pubmed
Vitelli,
Role of the small GTPase Rab7 in the late endocytic pathway.
1997,
Pubmed
Wang,
Rundown of NMDA-receptor mediated currents is resistant to lowering intracellular [Ca2+] and is prevented by ATP in rat spinal dorsal horn neurons.
1993,
Pubmed
Washbourne,
Rapid recruitment of NMDA receptor transport packets to nascent synapses.
2002,
Pubmed
Watt,
Activity coregulates quantal AMPA and NMDA currents at neocortical synapses.
2000,
Pubmed
Wenthold,
Trafficking of NMDA receptors.
2003,
Pubmed
Westphal,
Regulation of NMDA receptors by an associated phosphatase-kinase signaling complex.
1999,
Pubmed
Wiley,
Regulation of receptor tyrosine kinase signaling by endocytic trafficking.
2001,
Pubmed
Wyszynski,
Competitive binding of alpha-actinin and calmodulin to the NMDA receptor.
1997,
Pubmed
Xia,
An ER retention signal explains differences in surface expression of NMDA and AMPA receptor subunits.
2001,
Pubmed
Xu,
beta 1-adrenergic receptor association with the synaptic scaffolding protein membrane-associated guanylate kinase inverted-2 (MAGI-2). Differential regulation of receptor internalization by MAGI-2 and PSD-95.
2001,
Pubmed
Zerial,
Rab proteins as membrane organizers.
2001,
Pubmed
Zhang,
Calmodulin mediates calcium-dependent inactivation of N-methyl-D-aspartate receptors.
1998,
Pubmed
Zukin,
Alternatively spliced isoforms of the NMDARI receptor subunit.
1995,
Pubmed
von Zastrow,
Regulated endocytosis of opioid receptors: cellular mechanisms and proposed roles in physiological adaptation to opiate drugs.
2003,
Pubmed
