Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18

  title={Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18},
  author={Chien-Liang Glenn Lin and Irina Orlov and Alicia M. Ruggiero and Margaret Dykes‐Hoberg and Andy Lee and Mandy Jackson and Jeffrey D. Rothstein},
Excitatory amino-acid carrier 1 (EAAC1) is a high-affinity Na+-dependent l-glutamate/d, l-aspartate cell-membrane transport protein. It is expressed in brain as well as several non-nervous tissues. In brain, EAAC1 is the primary neuronal glutamate transporter. It has a polarized distribution in cells and mainly functions perisynaptically to transport glutamate from the extracellular environment. In the kidney it is involved in renal acidic amino-acid re-absorption and amino-acid metabolism… 
Changes in the expression of the glutamate transporter EAAT3/EAAC1 in health and disease
An overall picture of changes in EAAT3/EAAC1 expression in health and disease is provided and several mechanisms have been described for the rapid regulation of the membrane trafficking of the transporter.
Reticulon RTN2B Regulates Trafficking and Function of Neuronal Glutamate Transporter EAAC1*
It is shown that RTN2B, a member of the reticulon protein family that mainly localizes in the ER and ER exit sites interacts with EAAC1 and GTRAP3-18, and functions as a positive regulator in the delivery ofEAAC1 from the ER to the cell surface.
Modulation of neuronal glutathione synthesis by EAAC1 and its interacting protein GTRAP3-18
It is demonstrated that GTRAP3-18 regulates neuronal GSH level by controlling the EAAC1-mediated uptake of cysteine, which is much lower than that of glutamate or glycine and is the rate-limiting substrate for neurons GSH synthesis.
The Endoplasmic Reticulum Exit of Glutamate Transporter Is Regulated by the Inducible Mammalian Yip6b/GTRAP3-18 Protein*
It is demonstrated for the first time that GTRAP3-18 is a regulator of ER protein trafficking and uses hydrophobic domain interactions in the ER membrane to self-associate and cytoplasmic interactions at the C terminus to regulate trafficking.
Caveolin-1 Regulates the Delivery and Endocytosis of the Glutamate Transporter, Excitatory Amino Acid Carrier 1*
There is strong evidence that caveolin-1 contributes to the trafficking of EAAC1 on and off the plasma membrane and that these effects are associated with formation ofEAAC1-caveolin complexes.
Molecular pharmacology of glutamate transporters, EAATs and VGLUTs
Modulation of the Neural Glutamate Transporter EAAC1 by the Addicsin-interacting Protein ARL6IP1*
It is reported that ADP-ribosylation factor-like 6 interacting protein 1 (Arl6ip1) is a novel addicsin-associated partner that indirectly promotes EAAC1-mediated glutamate transport activity in a protein kinase C activity-dependent manner.


Primary structure and functional characterization of a high-affinity glutamate transporter
A complementary DNA encoding an electrogenic Na+ but not Cl−-dependent high-affinity glutamate transporter (named EAAC1) is isolated from rabbit small intestine by expression in Xenopus oocytes and transcripts are found in specific neuronal structures in the central nervous system as well as in the small intestine, kidney, liver and heart.
Multiple Signaling Pathways Regulate Cell Surface Expression and Activity of the Excitatory Amino Acid Carrier 1 Subtype of Glu Transporter in C6 Glioma
The studies suggest that the trafficking of the neuronal glutamate transporter EAAC1 is regulated by two independent signaling pathways and also may suggest a novel endogenous protective mechanism to limit glutamate-induced excitotoxicity.
EAAC1, a high-affinity glutamate tranporter, is localized to astrocytes and gabaergic neurons besides pyramidal cells in the rat cerebral cortex.
The localization of EAAC1 may explain the pathological symptoms that follow EAAC knockout (seizures and mild toxicity), as seizures could be due to the loss ofEAAC1-mediated fine regulation of neuronal excitability at axodendritic and axospinous synapses, whereas the mild toxicity may be related to the functional inactivation of astrocytic EAAC 1.
Localization of the high-affinity glutamate transporter EAAC1 in rat kidney.
Results are consistent with EAAC1 encoding the previously described apical high-affinity glutamate transporter in the kidney that mediates reabsorption of acidic amino acids in tubules beyond early proximal tubule S1 segments.
Differential synaptic localization of the glutamate transporter EAAC1 and glutamate receptor subunit gluR2 in the rat hippocampus
EAAC1, a neuron‐specific glutamate transporter, is likely to play an important role in the regulation of glutamate levels in the synaptic cleft. Ultrastructural studies have demonstrated that the
Platelet-derived Growth Factor Rapidly Increases Activity and Cell Surface Expression of the EAAC1 Subtype of Glutamate Transporter through Activation of Phosphatidylinositol 3-Kinase*
It is reported that platelet-derived growth factor (PDGF) increased Na+-dependentl-[3H]-glutamate transport activity within 30 min and it is possible that this PDGF-mediated increase in EAAC1 activity may contribute to the previously demonstrated neuroprotective effects of PDGF.
Localization of neuronal and glial glutamate transporters