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The Journal of Neuroscience, July 1, 2002, 22(13):5387-5392
Critical Postsynaptic Density 95/Disc Large/Zonula
Occludens-1 Interactions by Glutamate Receptor 1 (GluR1)
and GluR2 Required at Different Subcellular Sites
Antonella
Piccini and
Roberto
Malinow
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724
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ABSTRACT |
Interactions between AMPA receptor subunits and proteins containing
postsynaptic density 95/disc large/zonula occludens-1 (PDZ)
domains have been shown to play critical roles in the proper trafficking of receptors to excitatory synapses. Synaptic accumulation of AMPA receptors containing the glutamate receptor 1 (GluR1) subunit can be driven by calcium/calmodulin-dependent protein kinase II
activity or long-term potentiation and requires an interaction between
GluR1 and a type I PDZ domain-containing protein. Synaptic incorporation of AMPA receptors with only GluR2 occurs continuously, and this requires an interaction between GluR2 and a type II PDZ domain-containing protein. We used dual-channel, two-photon laser scanning microscopy to provide high-resolution visualization and quantification of green fluorescent protein-tagged AMPA receptors in
different subcellular compartments. We showed that mutations on GluR1
or GluR2 AMPA subunit that perturb interactions with PDZ domain
proteins lead to the accumulation of these receptors at different
subcellular sites. GluR1 mutants accumulate in the dendrite, whereas
GluR2 mutants accumulate in dendritic spines. This suggests that the
critical PDZ domain interactions are required for entry into spines for
GluR1 and for entry into synapses for GluR2.
Key words:
GluR1; GluR2; PDZ domain protein; two-photon laser
scanning imaging; dendrite; dendritic spine; organotypic slice
culture
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INTRODUCTION |
Excitatory synapses in the CNS
are found predominantly on dendritic spines, specialized postsynaptic
structures that protrude from dendritic shafts (Harris and Kater,
1994 ). AMPA-type receptors (AMPA-Rs) mediate most of the fast
excitatory synaptic transmission in the CNS, and a change in
AMPA-R-mediated transmission underlies several developmental and adult
forms of synaptic plasticity (Bliss and Collingridge, 1993; Linden and
Connor, 1995; Nicoll and Malenka, 1995; Wu et al., 1996; Bear and
Rittenhouse, 1999). Recent studies on the mechanisms controlling
synaptic plasticity have led to models that include rapid
redistribution of AMPA-Rs to or from synaptic sites (Carroll et al.,
1999; Luscher et al., 1999; Shi et al., 1999; Passafaro et al., 2001;
Malinow and Malenka, 2002). In these models, regulated insertion of
AMPA-Rs into synapses accounts for increased synaptic efficacy, whereas
regulated removal of synaptic AMPA-Rs accounts for decreased synaptic efficacy.
AMPA-Rs are hetero-oligomers composed of variable combinations of four
subunits, glutamate receptor 1 (GluR1)-GluR4 (also referred to
as GluRA-GluRD) (Seeburg, 1993; Hollmann and Heinemann, 1994;
Dingledine et al., 1999). In the hippocampus, GluR1, GluR2, and GluR3
predominate in adults, whereas GluR4 is primarily expressed early in
development (Zhu et al., 2000). In the adult hippocampus, the majority
of AMPA-Rs contain either GluR2 and GluR1 or GluR2 and GluR3 (Wenthold
et al., 1996) and the mature receptors are likely to contain four AMPA
subunits (Rosenmund et al., 1998). AMPA-R subunits have four
transmembrane domains, with a large extracellular N-terminal domain and
an intracellular C terminus. The extracellular domain and the four
membrane-associated domains show considerable homology among different
subunits. In contrast, the cytoplasmic C termini of these subunits are
either long (e.g., GluR1 and GluR4) or short (e.g., GluR2 and GluR3)
(Fig. 1). Receptors with long cytoplasmic C
termini are driven to synapses in a manner that requires synaptic NMDA
receptor activity (Shi et al., 1999; Hayashi et al., 2000; Zhu et al.,
2000; Passafaro et al., 2001). Significantly, the synaptic delivery of
GluR1 and GluR4 is governed by different processes, because synaptic
delivery of GluR1 is driven by CaMKII activity (Hayashi et al., 2000),
whereas synaptic delivery of GluR4 is driven by PKA activity (Esteban
and Malinow, 2001). In contrast to GluR1 and GluR4, receptors with only
short cytoplasmic tails incorporate into synapses in a manner
independent of synaptic activity (Shi et al., 2001). A number of
protein-protein interactions between cytosolic proteins and the C
termini of specific glutamate receptor subunits have been identified.
Among these, interactions with proteins containing postsynaptic density
95/disc large/zonula occludens-1 (PDZ) motifs appear to play a
central role in scaffolding receptors and signaling elements and have been shown to be important in the anchoring and delivery of the receptors to synapses (Ziff, 1997; Garner et al., 2000; Sheng and Sala,
2001; Malinow and Malenka, 2002). Previous electrophysiological studies
with recombinant receptors composed of GluR1 or GluR2 have shown that
PDZ domain interactions are critical for their incorporation into
synapses. However, it is not known at what subcellular sites these PDZ
domain interactions are required.
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Figure 1.
Dual-channel TPLSM imaging of CA1 pyramidal
neurons reveals both channel distribution and cell morphology.
A, Alignment of the cytoplasmic C termini of AMPA-R
subunits. Asterisks indicate identical residues;
dots indicate homologous residues.
Numbers indicate the amino acid number in GluR1 and
GluR2 without signal peptides. Some known sites for protein
interactions or phosphorylation are shown. B,
TPLSM of hippocampal CA1 pyramidal neurons expressing GluR1-GFP
(left): one infected cell was injected with Texas Red
dye (center), and images are merged
(right). Images shown are projections of several
sections acquired 1.5 µm apart. Scale bar, 50 µm. C,
High-magnification image of an apical dendrite from a neuron infected
with GluR1-GFP. The amount of receptor in a dendrite is compared with
the amount in an adjacent spine. The regions indicated on spine and
parental dendrite are typical examples of the ones selected for the
analysis. The image shown is a projection of several sections acquired
0.5 µm apart. Scale bar, 5 µm. D, Graph of mean
fluorescence of a typical small region (from a dendrite, in this case)
for the GFP (green) channel and the Texas Red
(red) channel plotted as a function of depth. The peak
of mean fluorescence and the correspondent background for each channel
used for image analysis are indicated.
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We used dual-channel, two-photon laser scanning microscopy (TPLSM) to
provide high-resolution visualization and quantification of AMPA-Rs in
different subcellular compartments. This method allowed us to determine
the relative amounts of AMPA-R located in the dendritic shaft or in an
adjacent dendritic spine. By monitoring the localization of various
mutant receptors, we showed that GluR1 mutant receptors lacking PDZ(I)
domain interactions displayed reduced accumulation in spines and
remained in dendritic shafts. In contrast, GluR2 mutant receptors
lacking PDZ(II) domain interactions show enhanced accumulation in
spines, despite their inability to incorporate stably into synapses
(Osten et al., 2000; Shi et al., 2001). Thus, these results suggest
that GluR1-PDZ interactions occur at the dendrite-spine border and
that GluR2-PDZ interactions occur at the spine-synapse interface.
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MATERIALS AND METHODS |
Recombinant receptors and expression. Constructs of
AMPA receptor subunits tagged with green fluorescent protein (GFP) were made as described previously (Hayashi et al., 2000; Shi et al., 2001).
Briefly, the GFP coding sequence (enhanced GFP; Clontech, Palo Alto,
CA) was inserted after the predicted signal peptide cleavage site of
the corresponding AMPA receptor subunit cDNA.
These constructs were expressed in CA1 neurons in rat organotypic
hippocampal slices using the Sindbis virus expression system. Slices
were prepared from postnatal 6- to 7-d-old animals, infected after 5-8
d in culture and imaged 2 d after the infection. Experiments were
performed at room temperature (22-25°C) in physiological ACSF (in
mM: 119 NaCl, 26 NaHCO3, 1 NaH2PO4, 11 D-glucose, 2.5 KCl, 2 CaCl2, 1.3 MgCl2, and 1.25 NaHPO4)
gassed with 5% CO2 and 95%
O2.
Two-photon microscopy. Before (20 min) imaging,
infected neurons were identified by fluorescence illumination and were
fully loaded (10-15 min after break-in) with a patch recording pipette (3-6 M ) containing 10 µM Texas Red
(sulforhodamine 101; Sigma, St. Louis, MO) in the internal
solution. The internal solution consisted of (in
mM): 115 K-gluconate, 10 HEPES, 2 MgCl2, 2 MgATP, 2 Na2ATP,
0.3 Na3GTP, and 20 KCl. Two-photon images were
collected on a custom-built instrument based on a Fluoview laser
scanning microscope (Olympus America, Melville, NY). The light
source was a mode-locked Ti:sapphire laser (Mira 900F, Santa Clara,
CA) running at 910 nm. We used a LUMPlanFl/IR 40× numerical
aperture 0.75 dipping lens. Each optical section was resampled
three times and typically was captured every 0.5 µm.
Image analysis. The borders of the locations defined as
spine and dendrite were selected using only the Texas Red channel image. No tagged GFP information was used at this stage to prevent any
unconscious bias. We then measured the GFP fluorescence in these
predefined dendritic and spinal compartments. The diffusional equilibration of a dye between the spinal compartment and the parental
dendritic shaft occurs in milliseconds (Svoboda et al., 1996).
Therefore, the Texas Red filling of the two structures was equilibrated
in the time scale of the experiment. We measured the mean intensity
fluorescence, as a function of z-dimension, in two small areas ( 2
µm2) over the dendrite and nearby spine.
Areas were drawn manually on each spine so as to enclose their
fluorescent signal. In the dendritic region at the base of the spine, a
region of similar size to the spine was chosen. The mean fluorescence
within each region was obtained using Fluoview 3.2 software (Olympus).
The subsequent analysis was performed with a custom-written software
program using the following approach: the peak of mean fluorescence per
area in the GFP channel and in the Texas Red channel for a particular
spine-dendrite pair was background subtracted, yielding the values
G and R, respectively. The background value is
the mean of the four values about the lowest fluorescence value obtained for a chosen region in each stack. The spine/dendrite ratio
(s/d) is then calculated as follows: s/d = [G/R]spine/[G/R]dend. For assessment of the statistically significant difference between two
sets of cumulative distributions, we used the Kolmogorov-Smirnov test.
For clarity, in the cumulative distribution plots, only the
x-axis (s/d) values <3 are shown (except see Fig.
4B). Because there were some s/d values >3, the
cumulative distributions shown do not always reach 100%. To examine
the exit of receptor from the cell body, the GFP fluorescence of
expressed GFP-tagged receptors was measured as a function of distance
from the cell body. Small areas (2
µm2) were drawn on the cell body and
along the primary dendrite every 10 µm. Values were background
subtracted and normalized by the intensity at the cell body and
averaged across cells. The background value was obtained for each cell
by choosing an area (2 µm2) on the
uninfected tissue nearby.
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RESULTS |
The subcellular distribution of AMPA-Rs plays a role in
determining synaptic strength and synaptic plasticity. To examine quantitatively the subcellular distribution of recombinant AMPA receptors, we injected pyramidal neurons expressing different GFP-tagged subunits with the freely diffusible marker, Texas Red (Fig.
1B). Our intent was to focus on the relative
distribution of AMPA-Rs at two sites: dendritic spines and dendritic
shafts just below spines (Fig. 1C). The distribution of
Texas Red reliably revealed neuronal morphology, as indicated by the
nearly identical distribution of Texas Red and plain GFP (Fig.
2C). As shown in Figure
2D, the ratios of signals in the GFP channel and
Texas Red channel (G/R) were nearly identical for
spines and dendritic regions. We have reported previously that AMPA-Rs
composed of GluR1-GFP appear to be restricted from dendritic spines
(Shi et al., 2001). This was concluded from the fact that neurons
expressing GluR1-GFP do not display a GFP signal that appears like
spines. We demonstrated this directly by showing that spines, as
revealed by filling with Texas Red, contain very little GluR1-GFP. To
quantify the relative distribution of GluR1, the ratios between the
green channel (GluR1-GFP) and the red channel (Texas Red) were
determined in both the spine and the underlying dendrite.
Significantly, the values for
[G/R]spine/[G/R]dend
are almost all <1 (Fig. 2D), arguing for a
restriction of GluR1-GFP from entering dendritic spines. In contrast
to GluR1-GFP, the signal for GluR2-GFP was clearly detectable in
dendritic spines, as reported previously (Shi et al., 2001) (Fig.
2B). The G/R values in spines
were not significantly different from those in dendrites (Fig.
2D). Importantly, the values
[G/R]spine/[G/R]dend
for GluR2-GFP were variable, much more than such values for plain GFP.
This indicates that GluR2-GFP was restricted from some spines and was
accumulated in others.
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Figure 2.
GluR1 and GluR2 show different
expression levels in spines. Dual-channel images of apical dendrites
show that GluR1-GFP appears restricted from dendritic spines
(A), whereas GluR2-GFP is detectable in
dendritic spines (B). Scale bar, 5 µm.
C, Dual-channel images of apical dendrites show that the
distribution of GFP and Texas Red are virtually identical. Scale bar, 5 µm. D, Cumulative distribution of the
[G/R]spine/[G/R]dend
fluorescence values GluR1-GFP are almostall <1. The GluR2-GFP
[G/R]spine/[G/R]dend
values are not significantly different from those in the dendrites
(spine-dendrite pairs: n = 41 for GluR1-GFP,
n = 36 for GluR2-GFP, and p = Kolmogorov-Smirnov test between GluR1-GFP and GluR2-GFP). Cumulative
distribution of the GFP
[G/R]spine/[G/R]dend
fluorescence values shows no difference between the two channels (s/d
~1; n = 24).
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We have shown previously, using electrophysiological methods, that
GluR1-GFP is driven into synapses by coexpression of a constitutively
active form of calcium/calmodulin-dependent protein kinase II (tCaMKII)
(Hayashi et al., 2000). We examined this phenomenon with imaging
methods to determine the extent of GluR1 redistribution in response to
increased CaMKII activity. The resulting images showed that a
significant amount of GluR1-GFP can be detected in spines. Thus,
although [G/R]spine is
less than [G/R]dend in neurons expressing GluR1-GFP, the
[G/R]spine is not
different from [G/R]dend
for neurons expressing both GluR1-GFP and tCaMKII. The cumulative
distribution of values for
[G/R]spine/[G/R]dend from cells expressing GluR1-GFP was significantly different from the
distribution of such values from cells expressing both GluR1-GFP and
tCaMKII. Indeed, the distribution of GluR1-GFP in cells coexpressing tCaMKII became indistinguishable from the distribution of GluR2-GFP (Fig. 3C).
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Figure 3.
Coexpression of GluR1-GFP and active  CaMKII
results in translocation of GluR1 into dendritic spines. However,
expression of GluR1(T887A)-GFP-IRES-tCaMKII does not result in
translocation of GluR1 into dendritic spines. A, In the
presence of active CaMKII, a significant amount of GluR1-GFP can be
visualized in spines. B, Little or no GluR1(T887A)-GFP
appears in dendritic spines in the presence of active CaMKII.
Scale bars: A, B, 5 µm. C,
Cumulative distributions of indicated constructs. Spine-dendrite
pairs: n = 88 for GluR1- GFP-IRES-tCaMKII,
n = 41 for GluR1-GFP, and n = 71 for GluR1(T887A)-GFP-IRES-tCaMKII; p values
provided for Kolmogorov-Smirnov test between indicated constructs.
GluR2-GFP from Figure 2, shown for comparison.
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Previous electrophysiological studies have indicated that GluR1
requires a group I PDZ domain interaction for tCaMKII to drive GluR1
into synapses (Hayashi et al., 2000). We tested whether this
interaction is required to move GluR1 from dendrites into spines or
from spines into synapses. We expressed GluR1-GFP(T887A), a mutant
subunit that forms a functional receptor and can prevent the
association with group I PDZ domain proteins, together with CaMKII
(Hayashi et al., 2000). As shown in Figure 3B, this mutation appears to prevent the receptor from entering dendritic spines. The
cumulative distribution of
[G/R]spine/[G/R]dend
values from cells expressing GluR1(T887A)-GFP and tCaMKII was not
significantly different from the distribution of the values from cells
expressing GluR1-GFP (p = 0.39) (Fig.
3C). In addition, the cumulative distribution of
[G/R]spine/[G/R]dend
values from cells expressing GluR1(T887A)-GFP and tCaMKII was
significantly different from the distribution of the values from cells
expressing GluR1-GFP-internal ribosome entry site
(IRES)-tCaMKII (p = 0.015) (Fig.
3C). We conclude that GluR1-PDZ(I) interaction is required
for tCaMKII to drive GluR1 from dendrite to spine.
We also investigated the trafficking of homomeric GluR2 receptors. We
have found previously that a group II PDZ domain interaction is
necessary for the continuous delivery of GluR2 to synapses. To localize
the subcellular compartment where the interaction between GluR2 and PDZ
domain II occurs, we focused on a mutant GluR2 with a tyrosine added at
the end of the C terminus (+863Y). This mutation prevents the
interaction between GluR2 and PDZ II domain-containing proteins (Xia et
al., 1999) and prevents incorporation of the receptor into synapses
(Shi et al., 2001). Surprisingly, although GluR2(+863Y)-GFP does not
incorporate into synapses, this receptor was clearly detected in spines
(Fig. 4A). Indeed, this
receptor shows increased accumulation in spines. The cumulative distribution of
[G/R]spine/[G/R]dend
values from cells expressing GluR2(+863Y)-GFP was greater than the
values obtained from cells expressing GluR2-GFP (Fig.
4B). This indicates that the amount of fluorescence
detected in the spines compared with the parent shaft was significantly
larger for the mutant than for the wild-type GluR2-GFP (Fig.
4B). This last finding suggests that
GluR2(+863Y)-GFP is able to enter the spine compartment and that the
interaction with the PDZ II domain required for delivery to the synapse
occurs in the spine.
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Figure 4.
The PDZ(II) domain mutant GluR2(+863Y) is
concentrated in spines. A, GluR2-GFP receptor is
clearly detected in spines. B, The amount of
fluorescence detected in the spines compared with the parent shaft is
significantly larger for the mutant than for the wild-type GluR2-GFP.
The cumulative distribution of
[G/R]spine/[G/R]dend
values from cells expressing GluR2(+863Y)-GFP is greater than the
values obtained from cells expressing GluR2-GFP (spine-dendrite
pairs: n = 20 for GluR2(+863Y),
n = 36 for GluR2-GFP; p = Kolmogorov-Smirnov test between GluR2(+863Y) and GluR2-GFP).
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In addition to the control of receptor distribution between dendrite
and spine, we also examined the general distribution of receptors
within a neuron. To examine this, we measured the intensity of the GFP
signal in the cell body and along the primary dendrite for each
receptor examined. As shown in Figure 5,
there was no detectable difference in the distribution of receptors from cell body to dendrite for any receptor examined in this study. Therefore, the exit of AMPA receptor from cell body to dendrite or the
retention within the dendrite does not appear to depend on the factors
considered in this study: GluR1, GluR2, CaMKII, or PDZ domain
interactions.
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Figure 5.
Trafficking of receptor from/to the cell body. The
intensity of the GFP signal along the primary dendrite (120 µm from
the cell body), normalized over the fluorescence of the cell body
(cb), was examined for each receptor.
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DISCUSSION |
The molecular mechanisms controlling the abundance of synaptic
ionotropic glutamate receptors seem to be a major site of regulation during plasticity (Malenka and Nicoll, 1997; Malinow, 1998; Luthi et
al., 1999; Garner et al., 2000; Sheng and Lee, 2001; Malinow and
Malenka, 2002). In particular, AMPA-Rs can be transported to and from
synapses, suggesting that receptor trafficking is a key factor in
regulating synaptic strength. Two types of AMPA-R trafficking processes
have been described: one is activity dependent, whereas the other is
continuous (Hayashi et al., 2000; Zhu et al., 2000; Passafaro et al.,
2001; Shi et al., 2001). GluR1/GluR2 receptors are added to synapses
during plasticity. This requires interactions between GluR1 and type I
PDZ domain proteins. In contrast, GluR2/3 receptors replace existing
synaptic receptors continuously. This occurs only at the synapses that
already have AMPA-Rs and requires interactions by GluR2 with
N-ethylmaleimide-sensitive factor (NSF) and type II PDZ
domain proteins. Interestingly, each trafficking process is distinct
and each seems ruled entirely by the specific molecular modules present
on the cytoplasmic C termini of a particular receptor subtype
(Passafaro et al., 2001; Shi et al., 2001). Although endogenous
receptors participating in activity-dependent trafficking are likely
GluR1/GluR2 heteromers, this trafficking appears to be closely mimicked
by recombinant homomeric GluR1 receptors (Passafaro et al., 2001; Shi
et al., 2001). Similarly, endogenous receptors participating in the
constitutive replacement are likely GluR2/GluR3 heteromers, and this
trafficking is well modeled by homomeric GluR2 receptors (Passafaro et
al., 2001; Shi et al., 2001).
In this study, we examined where, in neurons, these PDZ domain
interactions are required. Two potential sites of spatial regulation were considered: from cell body to dendrite and from dendrite to
dendritic spine. In none of our perturbations did we detect an effect
on the general distribution within the neuron. We thus conclude that
homomeric GluR2 or GluR1 receptors exit the cell body in equal amounts,
and that neither CaMKII activity nor PDZ domain interactions seem to
control this transition. This is in contrast to trafficking in
Caenorhabditis elegans, where CaMKII regulates the transport
of glutamate receptors from cell bodies to neurites (Rongo and Kaplan,
1999).
In contrast to the lack of effects on cell body to dendrite transition,
we find considerable regulation in the dendritic shaft to spine
transition. We confirm that GluR1 receptors are primarily excluded from
spines and that GluR2 receptors readily incorporate in spines (Shi et
al., 2001). Of interest, the distribution of GluR2-GFP in spines is
heterogeneous: some spines have relatively little, whereas others have
considerably more. This is consistent with the view that GluR2-GFP
receptors replace synaptic receptors (Shi et al., 2001) and that there
is normally a wide distribution in the amount of synaptic receptors
(Nusser et al., 1998; Petralia et al., 1999; Takumi et al., 1999). We
also confirm an effect, described electrophysiologically, that active
CaMKII can drive GluR1-containing AMPA-Rs into synapses (Hayashi et
al., 2000) by showing that active CaMKII drives GluR1-GFP into spines.
The most novel findings in this study concerned disruption of PDZ
domain interactions. We found that disruption of PDZ domain interaction(s) on GluR1 and GluR2 had different effects. For GluR1, the
(T887A) mutation prevented accumulation of this receptor into spines,
whereas for GluR2, the (+863Y) mutation enhanced accumulation of this
receptor into spines. These results indicate that PDZ domain
interactions by GluR1 and GluR2 are required at spatially distinct
sites. It is notable that GluR2 receptors with PDZ domain mutations
accumulate in spines (this study) and yet are not incorporated into
synapses (Shi et al., 2001). A similar phenotype has been described for
homomeric GluR3 receptors (Shi et al., 2001), which do have PDZ domains
but lack NSF-binding capacity. These phenotypes are consistent with the
view that the cytoplasmic tail of GluR2, NSF, and PDZ domain proteins
cooperates to form functionally important complexes (Hanley et al.,
2001).
A recent time-lapse study has indicated that the delivery processes
controlled by GluR1 or GluR2 may track through distinct subcellular
sites (Passafaro et al., 2001). In that study, GluR1 receptors were
delivered to the dendritic surface and then incorporated into spines.
In contrast, GluR2 receptors were delivered directly into the spine
surface. In this case, if PDZ domain interactions were important in
surface delivery, one would predict that mutant receptors lacking PDZ
ligand domains would accumulate at different subcellular sites. In
particular, GluR1 PDZ domain mutants should accumulate in dendrites and
not go into spines, whereas GluR2 PDZ domain mutants should accumulate
in spines. This is the distribution observed for our PDZ domain
mutants, suggesting that PDZ domain interactions are critical for
surface delivery of the receptors. This suggests that GluR1 and GluR2
are delivered to the surface by similar processes occurring at
fundamentally different sites.
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FOOTNOTES |
Received Jan. 16, 2002; revised March 25, 2002; accepted April 5, 2002.
This work was supported by the National Institutes of Health (R.M.). We
thank N. Dawkins-Pisani for technical help, B. Burbach and K. Svoboda
for help with the two-photon image acquisition, M. Reigl for writing
the image analysis program, Y. Hayashi and S.-H. Shi for constructs,
and P. Wasling and members of the Malinow lab for helpful discussions.
We thank T. Zador, S. Rumpel, and L. Van Aelst for comments on a
previous version of this manuscript.
Correspondence should be addressed to Roberto Malinow, Cold Spring
Harbor Laboratory, Cold Spring Harbor, NY 11724. E-mail: malinow{at}cshl.org.
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REFERENCES |
-
Bear MF,
Rittenhouse CD
(1999)
Molecular basis for induction of ocular dominance plasticity.
J Neurobiol
41:83-91[Web of Science][Medline].
-
Bliss TV,
Collingridge GL
(1993)
A synaptic model of memory: long-term potentiation in the hippocampus.
Nature
361:31-39[Medline].
-
Carroll RC,
Lissin DV,
von Zastrow M,
Nicoll RA,
Malenka RC
(1999)
Rapid redistribution of glutamate receptors contributes to long-term depression in hippocampal cultures.
Nat Neurosci
2:454-460[Web of Science][Medline].
-
Dingledine R,
Borges K,
Bowie D,
Traynelis SF
(1999)
The glutamate receptor ion channels.
Pharmacol Rev
51:7-61[Abstract/Free Full Text].
-
Esteban JA,
Malinow R
(2001)
A molecular mechanism for the regulated synaptic delivery of GluR4-containing AMPA receptors.
Soc Neurosci Abstr
27:20.
-
Garner CC,
Nash J,
Huganir RL
(2000)
PDZ domains in synapse assembly and signalling.
Trends Cell Biol
10:274-280[Web of Science][Medline].
-
Hanley JG,
Khatri L,
Hanson PI,
Ziff EB
(2001)
Regulation of AMPA receptor GluR2 subunit-PDZ protein interactions by NSF and -/
 -SNAPS.
Soc Neurosci Abstr
27:403. -
Harris KM,
Kater SB
(1994)
Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function.
Annu Rev Neurosci
17:341-371[Web of Science][Medline].
-
Hayashi Y,
Shi SH,
Esteban JA,
Piccini A,
Poncer JC,
Malinow R
(2000)
Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction.
Science
287:2262-2267[Abstract/Free Full Text].
-
Hollmann M,
Heinemann S
(1994)
Cloned glutamate receptors.
Annu Rev Neurosci
17:31-108[Web of Science][Medline].
-
Linden DJ,
Connor JA
(1995)
Long-term synaptic depression.
Annu Rev Neurosci
18:319-357[Web of Science][Medline].
-
Luscher C,
Xia H,
Beattie EC,
Carroll RC,
von Zastrow M,
Malenka RC,
Nicoll RA
(1999)
Role of AMPA receptor cycling in synaptic transmission and plasticity.
Neuron
24:649-658[Web of Science][Medline].
-
Luthi A,
Chittajallu R,
Duprat F,
Palmer MJ,
Benke TA,
Kidd FL,
Henley JM,
Isaac JT,
Collingridge GL
(1999)
Hippocampal LTD expression involves a pool of AMPARs regulated by the NSF-GluR2 interaction.
Neuron
24:389-399[Web of Science][Medline].
-
Malenka RC,
Nicoll RA
(1997)
Silent synapses speak up.
Neuron
19:473-476[Web of Science][Medline].
-
Malinow R
(1998)
Silencing the controversy in LTP?
Neuron
21:1226-1227[Medline].
-
Malinow R, Malenka R (2002) AMPA receptor trafficking and
synaptic plasticity. Annu Rev Neurosci, in press.
-
Nicoll RA,
Malenka RC
(1995)
Contrasting properties of two forms of long-term potentiation in the hippocampus.
Nature
377:115-118[Medline].
-
Nusser Z,
Lujan R,
Laube G,
Roberts JD,
Molnar E,
Somogyi P
(1998)
Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus.
Neuron
21:545-559[Web of Science][Medline].
-
Osten P,
Khatri L,
Perez JL,
Köhr G,
Giese G,
Daly C,
Schulz TW,
Wensky A,
Lee LM,
Ziff EB
(2000)
Mutagenesis reveals a role for ABP/GRIP binding to GluR2 in synaptic surface accumulation of the AMPA receptor.
Neuron
27:313-325[Web of Science][Medline].
-
Passafaro M,
Piech V,
Sheng M
(2001)
Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons.
Nat Neurosci
4:917-926[Web of Science][Medline].
-
Petralia RS,
Esteban JA,
Wang YX,
Partridge JG,
Zhao HM,
Wenthold RJ,
Malinow R
(1999)
Selective acquisition of AMPA receptors over postnatal development suggests a molecular basis for silent synapses.
Nat Neurosci
2:31-36[Web of Science][Medline].
-
Rongo C,
Kaplan JM
(1999)
CaMKII regulates the density of central glutamatergic synapses in vivo.
Nature
402:195-199[Medline].
-
Rosenmund C,
Stern-Bach Y,
Stevens CF
(1998)
The tetrameric structure of a glutamate receptor channel.
Science
280:1596-1599[Abstract/Free Full Text].
-
Seeburg PH
(1993)
The TINS/TiPS lecture: the molecular biology of mammalian glutamate receptor channels.
Trends Neurosci
16:359-365[Web of Science][Medline].
-
Sheng M,
Lee SH
(2001)
AMPA receptor trafficking and the control of synaptic transmission.
Cell
105:825-828[Web of Science][Medline].
-
Sheng M,
Sala C
(2001)
PDZ domains and the organization of supramolecular complexes.
Annu Rev Neurosci
24:1-29[Web of Science][Medline].
-
Shi S,
Hayashi Y,
Esteban JA,
Malinow R
(2001)
Subunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons.
Cell
105:331-343[Web of Science][Medline].
-
Shi SH,
Hayashi Y,
Petralia RS,
Zaman SH,
Wenthold RJ,
Svoboda K,
Malinow R
(1999)
Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation.
Science
284:1811-1816[Abstract/Free Full Text].
-
Svoboda K,
Tank DW,
Denk W
(1996)
Direct measurement of coupling between dendritic spines and shafts.
Science
272:716-719[Abstract].
-
Takumi Y,
Matsubara A,
Rinvik E,
Ottersen OP
(1999)
The arrangement of glutamate receptors in excitatory synapses.
Ann NY Acad Sci
868:474-482[Web of Science][Medline].
-
Wenthold RJ,
Petralia RS,
Blahos II J,
Niedzielski AS
(1996)
Evidence for multiple AMPA receptor complexes in hippocampal CA1/CA2 neurons.
J Neurosci
16:1982-1989[Abstract/Free Full Text].
-
Wu G,
Malinow R,
Cline HT
(1996)
Maturation of a central glutamatergic synapse.
Science
274:972-976[Abstract/Free Full Text].
-
Xia J,
Zhang X,
Staudinger J,
Huganir RL
(1999)
Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1.
Neuron
22:179-187[Web of Science][Medline].
-
Zhu JJ,
Esteban JA,
Hayashi Y,
Malinow R
(2000)
Postnatal synaptic potentiation: delivery of GluR4-containing AMPA receptors by spontaneous activity.
Nat Neurosci
3:1098-1106[Web of Science][Medline].
-
Ziff EB
(1997)
Enlightening the postsynaptic density.
Neuron
19:1163-1174[Web of Science][Medline].
Copyright © 2002 Society for Neuroscience 0270-6474/02/22135387-06$05.00/0
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ABSTRACT
INTRODUCTION
