The Journal of Neuroscience, July 2, 2003, 23(13):5589-5593
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BRIEF COMMUNICATION
Phorbol Myristate Acetate-Dependent Interaction of Protein Kinase C
and the Neuronal Glutamate Transporter EAAC1
Marco I. González,1,2
Peter G. Bannerman,1 and
Michael B. Robinson1,2
Departments of 1Pediatrics and
2Pharmacology, Children's Hospital of Philadelphia,
University of Pennsylvania, Philadelphia PA 19104-4318
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Abstract
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Sodium-dependent transporters clear extracellular glutamate in the
mammalian CNS. Activation of protein kinase C (PKC) rapidly increases the
activity of the neuronal glutamate transporter EAAC1 (excitatory amino acid
carrier-1). This effect is associated with redistribution of EAAC1 to the cell
membrane and appears to be dependent on a particular PKC subtype, PKC
.
In the present study, we sought to determine whether this specificity for
regulation of EAAC1 is associated with the formation of EAAC1–PKC
complexes. In C6 glioma cells, activation of PKC with phorbol 12-myristate
13-acetate (PMA) induced formation of EAAC1–PKC complexes but did
not induce formation of complexes with PKC
, a PKC not thought to
regulate EAAC1. Formation of these complexes was blocked by inhibitors of PKC.
Confocal microscopy revealed that PMA caused EAAC1 and PKC to
colocalize in clusters at or near the cell surface. The EAAC1–PKC
complexes were also observed in rat brain synaptosomes, demonstrating that
this interaction is not restricted to C6 cells. These data demonstrate that
EAAC1 and PKC interact in a PKC-dependent manner that is associated
with EAAC1 redistribution. Although PKC activation has been implicated in the
regulation of many different neurotransmitter transporters, this study
provides the first example of an interaction between a neurotransmitter
transporter and PKC. PKC also forms complexes with GluR2 (glutamate
receptor subunit 2) and causes a reduction in the levels of GluR2-containing
AMPA receptors at the plasma membrane. Together, these data suggest that
PKC may simultaneously trigger the redistribution of EAAC1 and
glutamate receptors.
Key words: glutamate transporter; EAAC1; trafficking; PKC; phorbol ester; C6 glioma
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Introduction
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Glutamate is the predominant excitatory neurotransmitter in the mammalian
CNS. An extracellular accumulation of glutamate and the consequent excessive
activation of glutamate receptors (GluRs) appears to contribute to the damage
observed in acute and chronic neurodegenerative disorders
(Choi, 1992
). Unlike some other
neurotransmitters, there is no evidence for extracellular metabolism of
glutamate; instead, extracellular levels are maintained by a family of
sodium-dependent transporters, including the following: GLAST [for
glutamate/aspartate transporter (EAAT1)], GLT-1 [for glutamate transporter-1
(EAAT2)], EAAC1 [for excitatory amino acid carrier-1 (EAAT3)], EAAT4 (for
excitatory amino acid transporter-4), and EAAT5
(Sims and Robinson, 1999;
Danbolt, 2001).
Glutamate transporters shape receptor responses by two different
mechanisms, binding and active uptake. Binding of glutamate to transporters
contributes to the fast component of glutamate removal from the synaptic
space. This mechanism requires a high density of transporter molecules
surrounding the synaptic cleft to effectively buffer free glutamate available
for receptor activation. Active transport is generally considered a slow
process compared with the rapid kinetics of some ion channels activated by
glutamate, with a turnover time of 
100 msec, but it appears to be fast
enough to shape the activation of other glutamate receptors, particularly
those that do not rapidly desensitize or those that couple to G-proteins
(Wadiche et al., 1995;
Conti and Weinberg, 1999;
Diamond, 2001). These
observations demonstrate that glutamate transporters are involved in the
regulation of synaptic transmission and raise the possibility that regulation
of transporters may modulate synaptic transmission.
The activity of most of the glutamate transporters can be regulated by
mechanisms that are independent of de novo transporter synthesis
(Sims and Robinson, 1999;
Danbolt, 2001). In some cases,
the changes in activity are associated with insertion or removal of
transporter molecules at the plasma membrane. In C6 glioma, activation of
protein kinase C (PKC) rapidly (within minutes) increases EAAC1-mediated
transport activity. This effect is associated with a redistribution of EAAC1
from subcellular compartments to the plasma membrane
(Davis et al., 1998). Using
pharmacological approaches combined with downregulation of specific PKC
subtypes, we recently developed evidence to suggest that PKC regulates
EAAC1 redistribution and that PKC
regulates EAAC1 catalytic efficiency
(González et al.,
2002). As a first step in the characterization of the involvement
of PKC in the regulation of EAAC1 trafficking, we determined whether
EAAC1 and PKC interact. In the present study, we provide evidence for
an interaction between PKC and EAAC1 that is dependent on PKC
activation.
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Materials and Methods
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Cell culture. C6 glioma cells, a cell line that endogenously
expresses EAAC1 and none of the other transporter subtypes, were grown as
described previously (Davis et al.,
1998).
Preparation of crude synaptosomes. Synaptosomes were prepared from
adult rats and resuspended in 5 vol (v/w) of sucrose as described previously
(Robinson, 1998). Crude
synaptosomes (100 µl containing 500 µg of protein) were resuspended
in 900 µl of sodium containing buffer
(González et al.,
2002). PKC inhibitors or vehicle were added, and the synaptosomal
suspension was prewarmed to 37°C for 5 min. Phorbol 12-myristate
13-acetate (PMA) (100 nM) was added, and the synaptosomal
suspension was kept at 37°C for an additional 30 min. Synaptosomal
membranes were recovered by centrifugation at 20,000 x g for 20
min.
Immunoprecipitation and Western blot. C6 cells or synaptosomal
pellets were resuspended in 1 ml of lysis buffer
(González et al., 2002)
and solubilized for 1 hr at 4°C. Lysates were centrifuged at 12,500 rpm to
remove cell debris. Supernatants were precleared with 40 µl of protein
A-agarose beads (Invitrogen, Grand Island, NY) and gently shaken for 1 hr at
4°C. After centrifugation, an aliquot was saved, and the precleared
lysates were incubated overnight with 2 µg (C6 cells) or 3 µg
(synaptosomes) of affinity-purified polyclonal rabbit anti-EAAC1 antibody
[Alpha Diagnostics International (ADI), San Antonio, TX] at 4°C. Immune
complexes were collected after incubation for 2 hr with 30 µl of protein
A-agarose slurry. After four washes with lysis buffer, immune complexes were
released in 25 µl of 2x sample buffer by boiling at
90–95°C. Immunoprecipitated proteins were resolved by SDS-PAGE and
transferred to polyvinylidene difluoride membranes (Millipore, Bedford, MA).
After blocking, membranes were probed with antibodies for PKC (monoclonal
mouse anti-PKC at 1:500, Transduction Laboratories, San Diego, CA;
rabbit polyclonal anti-PKC at 1:2000, Santa Cruz Biotechnology, Santa
Cruz, CA) or EAAC1 (1:5000) and visualized with chemiluminescence.
Immunocytochemistry and confocal microscopy. C6 glioma (plated on
glass coverslips) were treated with vehicle or PMA (100 nM) for 30
min, washed with PBS, and fixed with 2% paraformaldehyde for 10 min. After
incubation with blocking solution (minimum essential medium containing 15
mM HEPES buffer, 10% fetal bovine serum, and 0.05% sodium azide)
for 10 min, anti-EAAC1 (1.25 µg/ml) and mouse anti-PKC (5 µg/ml)
were added for 30 min. Cultures were then incubated with biotinylated donkey
anti-rabbit Ig (species specific, 1:100) and rhodamine conjugated donkey
anti-mouse Ig (species specific, 1:100) for 30 min, followed by
fluorescein-conjugated streptavidin (1:100; all reagents from Jackson
ImmunoResearch, West Grove, PA) for 20 min. Coverslips were washed between
steps with PBS, postfixed with cold methanol for 8 min, and counterstained
with Hoechst H 33258 in PBS (2 µg/ml) for 3 min. Stained cells were mounted
in Vectorshield (Vector Laboratories, Burlingame, CA). Immunolabeled cultures
were optically sectioned at 0.5 µm intervals with a Leica (Nussloch,
Germany) Inverted DM IRE2 HC fluo TCS 1-B-UV microscope coupled to a Leica TCS
SP2 spectral confocal system/UV. Controls were run to confirm that the
staining was dependent on primary antibodies.
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Results
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EAAC1 associates with PKC in C6 cells treated with PMA
Activation of PKC increases the activity and cell surface expression of the
glutamate transporter EAAC1 (Davis et al.,
1998). Two lines of evidence suggested that PKC is required
for EAAC1 redistribution (González
et al., 2002). In the present study, we tested for possible
interactions between EAAC1 and PKC. Using an EAAC1-specific antibody,
essentially no PKC immunoreactivity was detected in immunoprecipitates
from control cells; however, treatment of C6 glioma with PMA (100
nM) for 30 min consistently resulted in the recovery of PKC
in EAAC1 immunoprecipitates (Fig.
1A). The increase in PKC immunoreactivity after
PMA treatment was not associated with any difference in the amount of EAAC1
recovered in the immunoprecipitates (Fig.
1A, bottom). The specificity of the
EAAC1–PKC interaction is supported by the absence of PKC
immunoreactivity when an irrelevant antibody (anti-GLT-1; ADI) was used or
when the EAAC1 antibody was omitted from the immunoprecipitation procedure
(Fig. 1A). In
addition, preabsorption of the anti-EAAC1 antibody with the corresponding
antigenic peptide (ADI) abolished PKC immunoreactivity
(Fig. 1B). Finally,
PKC was coimmunoprecipitated using an anti-EAAC1 antibody obtained from
a different source (Fig.
1C). To determine whether EAAC1 specifically associates
with PKC, immunoprecipitates were probed with antibodies to PKC,
and, under these conditions, no specific PKC immunoreactivity was
observed (Fig. 1D),
suggesting that that PKC activation with PMA induces the formation of a
specific EAAC1–PKC interaction. We also attempted to determine
whether PKC is present in EAAC1 immunoprecipitates, but none was
detected (data not shown; n = 3). Because the levels of PKC
immunoreactivity are relatively low in C6 glioma
(González et al.,
2002), we cannot conclusively rule out the possibility that there
is a complex but that it is not detectable under the current conditions.
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Figure 1. EAAC1 associates with PKC in C6 glioma cells. A,
Coimmunoprecipitation of PKC with EAAC1 in C6 glioma cells stimulated
with PMA. C6 cells were treated with vehicle or PMA (100 nM) for 30
min. Cell lysates were immunoprecipitated (IP) with an anti-EAAC1 antibody,
anti-GLT-1 antibody, or no antibody. Immune complexes were recovered and
probed for PKC immunoreactivity (WB: PKC). B, Effect of
EAAC1 antibody preabsorption with the antigenic peptide. EAAC1 antibody (2
µg) was preabsorbed with 25µg of the corresponding peptide for 2 hr at
room temperature. Preabsorbed or non-preabsorbed antibody (IP) was incubated
overnight with C6 cells lysate. After recovery, immune complexes were assayed
for PKC immunoreactivity. C, Coimmunoprecipitation of
PKC with EAAC1 using a different anti-EAAC1 antibody. Vehicle- and PMA
(100 nM)-treated C6 cells lysates were immunoprecipitated (IP) with
an EAAC1 antibody from a different source (Dr. Rothstein, Johns Hopkins
University, Baltimore, MD), and the immunoprecipitates were assayed for
PKC immunoreactivity. D, PMA treatment does not induce the
interaction of EAAC1 with PKC. C6 cell lysates were immunoprecipitated
with an anti-EAAC1 antibody, anti-GLT-1 antibody, or no antibody (IP). The
immune complexes were probed for PKC immunoreactivity. All blots were
stripped and reprobed for EAAC1 immunoreactivity (WB: EAAC1) and are
representative of three independent experiments.
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PKC inhibitors prevent the formation of EAAC1–PKC
complexes
The increase in EAAC1 cell surface expression induced by PMA is abolished
by either bisindolylmaleimide II (BIS II), a general PKC inhibitor, or by
Gö6976, a selective inhibitor of the classical subtypes of PKC at low
micromolar concentrations (Davis et al.,
1998; González et al.,
2002). Therefore, the effects of PKC inhibitors on formation of
EAAC1–PKC complexes were examined. Either BIS II (10
µM) or Gö6976 (10 µM) prevented the
PMA-dependent formation of EAAC1–PKC complexes
(Fig. 2A). As a
control, we confirmed that these treatments did not affect the levels of EAAC1
in the immunoprecipitates or the levels of PKC in the cell lysates
(Fig. 2A, middle,
bottom). Together, these results strongly suggest that PKC activation is
required for formation of EAAC1–PKC complexes. Because PKC
is the only classical (Gö6976-sensitive) PKC detectable in C6 cells
(González et al.,
2002), these data suggest that PKC activation is
required.
Previously, we showed that activation of the platelet-derived growth factor
(PDGF) receptor increases the activity and cell surface expression of EAAC1
(Sims et al., 2000). These
effects are not blocked by the PKC antagonist BIS II and appear to be
independent of PKC activation. Treatment of C6 cells with PDGF did not induce
formation of EAAC1–PKC complexes
(Fig. 2B), suggesting
that formation of the complex is specific and is not simply related to
redistribution of EAAC1.
EAAC1 and PKC colocalize in C6 cells after PKC activation
Based on these studies, it is not clear whether this complex exists within
the cell or at the cell surface. In several different experiments, we
attempted to combine biotinylation of cell surface proteins with
immunoprecipitation, but we were unable to free the biotinylated transporters
from avidin beads with excess biotin. Therefore, we used confocal microscopy
to determine whether EAAC1 and PKC colocalize after activation of PKC.
In optical cross-sections of the midsection of the cell, the bulk of EAAC1
immunoreactivity (green) was evenly distributed throughout the interior of the
cell, and PKC immunostaining (red) was predominantly detected in a
perinuclear compartment under control conditions
(Fig. 3). After PMA treatment,
there was a decrease in the intracellular labeling for EAAC1 and PKC,
and both proteins were located at or near the plasma membrane, in which they
appear to form clusters and colocalize (yellow). As observed previously, PMA
treatment also changed the morphology and increased the "ruffling"
of the cells (Davis et al.,
1998). It is known that activation of PKC with PMA is associated
with the translocation of PKC to the cell membrane. Therefore, it is not
surprising that these two plasma membrane-trafficked proteins colocalize at
the cell membrane after PMA treatment. The fact that we do not observe
significant intracellular colocalization, along with the data that support the
formation of complexes between these two proteins, is consistent with the
notion that EAAC1 and PKC interact at or near the cell membrane.
EAAC1 associates with PKC in brain tissue
To determine whether the association of EAAC1 and PKC occurs in
vivo, EAAC1 was immunoprecipitated from rat cortical synaptosomes. In
contrast to our in vitro observations with C6 cells (in which
EAAC1–PKC complexes were not detectable in the absence of PMA),
PKC immunoreactivity was detected in EAAC1 immunoprecipitates in the
absence of exogenous PKC activation (Fig.
4A, B). The PKC antagonist BIS II (10 µM)
dramatically reduced the amount of PKC detected, suggesting that
endogenous PKC activation causes formation of the complex. The observation
that much lower levels of PKC are detected when synaptosomes are not
incubated at 37°C and that this signal increases with length of incubation
at 37°C (Fig. 4C)
suggests that formation of the complex was triggered during the incubation
period. In addition, exogenous activation of PKC with PMA increased the signal
for PKC immunoreactivity, and the PKC antagonist BIS II blocked this
effect (Fig. 4A, B).
The changes in PKC immunoreactivity are not produced by a change in the
efficiency of the immunoprecipitation, because the amount of EAAC1
immunoreactivity recovered under all conditions was similar (data not shown).
To determine whether the formation of EAAC1–PKC complexes is
restricted to cortex, EAAC1 was immunoprecipitated from synaptosomes prepared
from several brain regions. PKC was detected in EAAC1
immunoprecipitates from cerebellum, hippocampus, and midbrain
(Fig. 4D). In these
regions, application of BIS II (10 µM) reduced the basal complex
formation and also prevented the formation of complex induced by exogenous PKC
activation. In brainstem, in which the levels of expression for EAAC1 and
PKC were relatively low, PKC was not detected (data not shown).
These results show that the formation of the EAAC1–PKC complex is
detectable in synaptosomes and that endogenous stimuli can also result in
formation of this complex.
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Discussion
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Previously, we showed that inhibition of PKC with Gö6976
reduces the PMA-induced increase in EAAC1-mediated activity. Gö6976
abolishes the increase in EAAC1 cell surface expression in C6 glioma and in
primary neuronal cultures. In addition, selective downregulation of the PKC
subtypes expressed in C6 cells suggests a specific role for PKC in the
regulation of EAAC1 trafficking
(González et al.,
2002). The specific events involved in EAAC1 redistribution are
unknown, but if the involvement of PKC in EAAC1 redistribution is
dependent on phosphorylation of EAAC1 or of an adapter-protein involved in
EAAC1 trafficking, the association of EAAC1 and PKC in a multiprotein
complex may be necessary. In C6 cells, treatment with PMA promoted an
interaction between EAAC1 and PKC. This effect was blocked by PKC
antagonists, suggesting that the formation of the complex requires PKC
activation. In rat brain synaptosomes, the EAAC1–PKC association
was detected in the absence of PMA, and PMA induced an additional increase in
the recovery of PKC immunoreactivity. Both effects were blocked by a
PKC antagonist, suggesting that the association may be triggered by endogenous
stimulation of PKC activity under physiological and/or pathological
conditions.
Several members of the neurotransmitter transporter family are regulated by
kinases, phosphatases, and interacting proteins; however, the mechanisms
involved in this regulation are unknown. All of the neurotransmitter
transporters contain intracellular consensus sequences for phosphorylation,
and there is evidence that many members of this family are phosphorylated. In
addition, there is some evidence that direct phosphorylation of transporters
may be required for the regulation of transporter activity and/or cell surface
expression (Blakely and Bauman,
2000; Danbolt,
2001; Foster et al.,
2002). Because EAAC1 and PKC interact, this raises the
possibility that, after interaction, PKC may directly phosphorylate
EAAC1 and promote its redistribution. In preliminary studies using C6 cells
metabolically labeled with [32P]orthophosphate, we found that PKC
activation with PMA promotes the phosphorylation of immunoprecipitable EAAC1,
and this effect is blocked by BIS II (data not shown; n = 3),
suggesting that PKC phosphorylates EAAC1. However, these data do not prove
that direct phosphorylation is required for the regulation of transporter
activity or trafficking. An alternative is that PKC phosphorylates an
accessory protein that in turn regulates the activity and/or cell surface
expression of EAAC1. Finally, it is also possible that the interaction is
independent of the phosphorylation of EAAC1 or an adapter protein and that
activated PKC simply has a higher affinity for EAAC1 (or an adapter
protein); however, we have not determined whether the PKC in the
complex is catalytically active.
Recently, some proteins that interact with neurotransmitter transporters
have been described, and these interactions may either influence PKC signaling
or are influenced by PKC signaling. For example, PKC activation modulates an
interaction between syntaxin 1A and the 
-aminobutyric acid transporter
GAT-1. This interaction appears to regulate both the cellular distribution and
catalytic efficiency of GAT-1 (Deken et
al., 2000; Horton and Quick,
2001). The PDZ (for postsynaptic density-95/Discs large/zona
occludens-1) domain-containing protein PICK1 (for protein interacting with C
kinase 1) and the LIM (for Lin-11, Isl-1, and Mec-3) domain-containing protein
Hic-5 interact with the dopamine transporter, and these scaffolding proteins
may recruit activated PKC and/or focal adhesion kinase to regulate transporter
activity or cell surface expression
(Torres et al., 2001;
Carneiro et al., 2002).
Finally, the catalytic subunit of the protein phosphatase 2A has been detected
in complexes with the serotonin, norepinephrine, and dopamine transporters.
PKC activation results in phosphorylation and sequestration of the serotonin
transporter and disrupts the interaction of protein phosphatase 2A with this
transporter (Bauman et al.,
2000). Despite these efforts, there is currently no evidence that
PKC is part of these complexes.
Some proteins that interact with glutamate transporters have also been
described recently. These proteins include a member of the LIM family, Ajuba,
that associates with GLT-1 (Marie et al.,
2002). GTRAP3–18 (glutamate transporter associated protein
3–18) (Lin et al., 2001)
and GTRAP48 (Jackson et al.,
2001) interact with and regulate the activities of EAAC1 and
EAAT4, respectively. In the present study, we describe a novel interaction
between the glutamate transporter EAAC1 and PKC. Although we have
evidence that PKC activation may be required for EAAC1 redistribution
(González et al.,
2002), at present it is not clear how this interaction might
regulate EAAC1 trafficking. Because most cell types express multiple PKC
subtypes, it is possible that the interaction simply permits specific
regulation of EAAC1 by PKC. It is also possible that the interaction
may alter the rate of recycling and stabilize EAAC1 at the cell membrane.
Finally, more complicated models are suggested by the observation that
PKC activation alters both the redistribution of 
1-integrin to
the cell surface and its endocytosis, with both effects apparently dependent
on PKC–1-integrin association
(Ng et al., 1999).
Activation of PKC has also been implicated in the regulation of cell
surface levels of AMPA receptors containing the GluR2 subunit. After PMA
application, activated PKC is directed to neuronal spines in which
GluR2-containing AMPA receptors are located. Here, PKC and GluR2
interact and AMPA receptors are internalized after phosphorylation. A
reduction in the number of postsynaptic AMPA receptors has been implicated as
one of the crucial factors for the induction of long-term depression
(Barry and Ziff, 2002;
Malinow and Malenka, 2002). In
hippocampus, GluR2 and EAAC1 are present in the dendritic membranes. Although
EAAC1 is not intermixed with GluR2, it is present perisynaptically,
immediately outside the synaptic specialization ideally located to restrict
the action of glutamate within the precise site of synaptic communication
(He et al., 2000). In fact,
these transporters are thought to limit the "spillover" between
synapses in area CA1 of the hippocampus
(Diamond, 2001), and
regulation of glutamate transporters has been implicated in long-term
potentiation and long-term depression
(Brasnjo and Otis, 2001;
Levenson et al., 2001). These
observations raise the possibility that concerted regulation of receptors and
transporters may be a necessary step for the induction of synaptic plasticity.
Because activation of the same signaling molecule promotes the redistribution
of both GluR2-containing AMPA receptors and the neuronal transporter EAAC1, it
is possible that coordinate regulation of transporters and receptors may be
required to trigger synaptic plasticity.
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Footnotes
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Received Mar. 26, 2003;
revised May. 5, 2003;
accepted May. 7, 2003.
This work was supported by National Institutes of Health Grants NS29868 and
NS39011. We thank Dr. Jeff Rothstein for generously providing anti-EAAC1
antibody.
Correspondence should be addressed to Dr. Michael B. Robinson, 502N
Abramson Pediatric Research Building, 3615 Civic Center Boulevard,
Philadelphia, PA 19104-4318. E-mail:
robinson{at}pharm.med.upenn.edu.
Parts of this paper have been published previously in abstract form
(González and Robinson,
2002).
Copyright © 2003 Society for Neuroscience
0270-6474/03/235589-05$15.00/0
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M. Watabe, K. Aoyama, and T. Nakaki
Regulation of Glutathione Synthesis via Interaction between Glutamate Transport-Associated Protein 3-18 (GTRAP3-18) and Excitatory Amino Acid Carrier-1 (EAAC1) at Plasma Membrane
Mol. Pharmacol.,
November 1, 2007;
72(5):
1103 - 1110.
[Abstract]
[Full Text]
[PDF]
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M. I. Gonzalez, E. Krizman-Genda, and M. B. Robinson
Caveolin-1 Regulates the Delivery and Endocytosis of the Glutamate Transporter, Excitatory Amino Acid Carrier 1
J. Biol. Chem.,
October 12, 2007;
282(41):
29855 - 29865.
[Abstract]
[Full Text]
[PDF]
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J. D. Pita-Almenar, M. S. Collado, C. M. Colbert, and A. Eskin
Different Mechanisms Exist for the Plasticity of Glutamate Reuptake during Early Long-Term Potentiation (LTP) and Late LTP
J. Neurosci.,
October 11, 2006;
26(41):
10461 - 10471.
[Abstract]
[Full Text]
[PDF]
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Y. Huang and Z. Zuo
Isoflurane Induces a Protein Kinase C {alpha}-Dependent Increase in Cell-Surface Protein Level and Activity of Glutamate Transporter Type 3
Mol. Pharmacol.,
May 1, 2005;
67(5):
1522 - 1533.
[Abstract]
[Full Text]
[PDF]
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L. A. Johnson, B. Guptaroy, D. Lund, S. Shamban, and M. E. Gnegy
Regulation of Amphetamine-stimulated Dopamine Efflux by Protein Kinase C {beta}
J. Biol. Chem.,
March 25, 2005;
280(12):
10914 - 10919.
[Abstract]
[Full Text]
[PDF]
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M. E. R. Butchbach, G. Tian, H. Guo, and C.-l. G. Lin
Association of Excitatory Amino Acid Transporters, Especially EAAT2, with Cholesterol-rich Lipid Raft Microdomains: IMPORTANCE FOR EXCITATORY AMINO ACID TRANSPORTER LOCALIZATION AND FUNCTION
J. Biol. Chem.,
August 13, 2004;
279(33):
34388 - 34396.
[Abstract]
[Full Text]
[PDF]
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K. M. Fournier, M. I. Gonzalez, and M. B. Robinson
Rapid Trafficking of the Neuronal Glutamate Transporter, EAAC1: EVIDENCE FOR DISTINCT TRAFFICKING PATHWAYS DIFFERENTIALLY REGULATED BY PROTEIN KINASE C AND PLATELET-DERIVED GROWTH FACTOR
J. Biol. Chem.,
August 13, 2004;
279(33):
34505 - 34513.
[Abstract]
[Full Text]
[PDF]
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A. Kalandadze, Y. Wu, K. Fournier, and M. B. Robinson
Identification of Motifs Involved in Endoplasmic Reticulum Retention-Forward Trafficking of the GLT-1 Subtype of Glutamate Transporter
J. Neurosci.,
June 2, 2004;
24(22):
5183 - 5192.
[Abstract]
[Full Text]
[PDF]
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M. I. Gonzalez and M. B. Robinson
Protein KINASE C-Dependent Remodeling of Glutamate Transporter Function
Mol. Interv.,
February 1, 2004;
4(1):
48 - 58.
[Abstract]
[Full Text]
[PDF]
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M. B. Robinson
Signaling Pathways Take Aim at Neurotransmitter Transporters
Sci. Signal.,
November 4, 2003;
2003(207):
pe50 - pe50.
[Abstract]
[Full Text]
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Top
Abstract
Introduction
