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J Biol Chem
2011 Feb 04;2865:3935-43. doi: 10.1074/jbc.M110.187492.
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Hetero-oligomerization of neuronal glutamate transporters.
Nothmann D
,
Leinenweber A
,
Torres-Salazar D
,
Kovermann P
,
Hotzy J
,
Gameiro A
,
Grewer C
,
Fahlke C
.
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Excitatory amino acid transporters (EAATs) mediate the uptake of glutamate into neuronal and glial cells of the mammalian central nervous system. Two transporters expressed primarily in glia, EAAT1 and EAAT2, are crucial for glutamate homeostasis in the adult mammalian brain. Three neuronal transporters (EAAT3, EAAT4, and EAAT5) appear to have additional functions in regulating and processing cellular excitability. EAATs are assembled as trimers, and the existence of multiple isoforms raises the question of whether certain isoforms can form hetero-oligomers. Co-expression and pulldown experiments of various glutamate transporters showed that EAAT3 and EAAT4, but neither EAAT1 and EAAT2, nor EAAT2 and EAAT3 are capable of co-assembling into heterotrimers. To study the functional consequences of hetero-oligomerization, we co-expressed EAAT3 and the serine-dependent mutant R501C EAAT4 in HEK293 cells and Xenopus laevis oocytes and studied glutamate/serine transport and anion conduction using electrophysiological methods. Individual subunits transport glutamate independently of each other. Apparent substrate affinities are not affected by hetero-oligomerization. However, polarized localization in Madin-Darby canine kidney cells was different for homo- and hetero-oligomers. EAAT3 inserts exclusively into apical membranes of Madin-Darby canine kidney cells when expressed alone. Co-expression with EAAT4 results in additional appearance of basolateral EAAT3. Our results demonstrate the existence of heterotrimeric glutamate transporters and provide novel information about the physiological impact of EAAT oligomerization.
Amara,
Excitatory amino acid transporters: keeping up with glutamate.
2002, Pubmed
Amara,
Excitatory amino acid transporters: keeping up with glutamate.
2002,
Pubmed
Bendahan,
Arginine 447 plays a pivotal role in substrate interactions in a neuronal glutamate transporter.
2000,
Pubmed
,
Xenbase
Cheng,
A novel sorting motif in the glutamate transporter excitatory amino acid transporter 3 directs its targeting in Madin-Darby canine kidney cells and hippocampal neurons.
2002,
Pubmed
Danbolt,
Glutamate uptake.
2001,
Pubmed
Detro-Dassen,
Conserved dimeric subunit stoichiometry of SLC26 multifunctional anion exchangers.
2008,
Pubmed
,
Xenbase
Estévez,
Barttin is a Cl- channel beta-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion.
2001,
Pubmed
,
Xenbase
Fairman,
An excitatory amino-acid transporter with properties of a ligand-gated chloride channel.
1995,
Pubmed
,
Xenbase
Furuta,
Glutamate transporter protein subtypes are expressed differentially during rat CNS development.
1997,
Pubmed
Furuta,
Cellular and synaptic localization of the neuronal glutamate transporters excitatory amino acid transporter 3 and 4.
1997,
Pubmed
Gendreau,
A trimeric quaternary structure is conserved in bacterial and human glutamate transporters.
2004,
Pubmed
,
Xenbase
Grewer,
Glutamate translocation of the neuronal glutamate transporter EAAC1 occurs within milliseconds.
2000,
Pubmed
Grewer,
Individual subunits of the glutamate transporter EAAC1 homotrimer function independently of each other.
2005,
Pubmed
Haugeto,
Brain glutamate transporter proteins form homomultimers.
1996,
Pubmed
Janssen,
Disease-causing dysfunctions of barttin in Bartter syndrome type IV.
2009,
Pubmed
Koch,
The glutamate-activated anion conductance in excitatory amino acid transporters is gated independently by the individual subunits.
2007,
Pubmed
,
Xenbase
Koch,
Small-scale molecular motions accomplish glutamate uptake in human glutamate transporters.
2005,
Pubmed
,
Xenbase
Kovermann,
A conserved aspartate determines pore properties of anion channels associated with excitatory amino acid transporter 4 (EAAT4).
2010,
Pubmed
Leary,
The glutamate and chloride permeation pathways are colocalized in individual neuronal glutamate transporter subunits.
2007,
Pubmed
,
Xenbase
Levy,
Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake.
1998,
Pubmed
Lohi,
Functional characterization of three novel tissue-specific anion exchangers SLC26A7, -A8, and -A9.
2002,
Pubmed
,
Xenbase
Melzer,
Glutamate modifies ion conduction and voltage-dependent gating of excitatory amino acid transporter-associated anion channels.
2003,
Pubmed
Melzer,
A dynamic switch between inhibitory and excitatory currents in a neuronal glutamate transporter.
2005,
Pubmed
Mim,
Two conformational changes are associated with glutamate translocation by the glutamate transporter EAAC1.
2007,
Pubmed
Mim,
The glutamate transporter subtypes EAAT4 and EAATs 1-3 transport glutamate with dramatically different kinetics and voltage dependence but share a common uptake mechanism.
2005,
Pubmed
Nicke,
P2X1 and P2X3 receptors form stable trimers: a novel structural motif of ligand-gated ion channels.
1998,
Pubmed
,
Xenbase
Reyes,
Transport mechanism of a bacterial homologue of glutamate transporters.
2009,
Pubmed
Robertson,
Design, function and structure of a monomeric ClC transporter.
2010,
Pubmed
Tanaka,
Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1.
1997,
Pubmed
Torres-Salazar,
Neuronal glutamate transporters vary in substrate transport rate but not in unitary anion channel conductance.
2007,
Pubmed
,
Xenbase
Torres-Salazar,
Intersubunit interactions in EAAT4 glutamate transporters.
2006,
Pubmed
,
Xenbase
Trotti,
Inhibition of the glutamate transporter EAAC1 expressed in Xenopus oocytes by phorbol esters.
2001,
Pubmed
,
Xenbase
Veruki,
Activation of a presynaptic glutamate transporter regulates synaptic transmission through electrical signaling.
2006,
Pubmed
Wadiche,
Ion fluxes associated with excitatory amino acid transport.
1995,
Pubmed
,
Xenbase
Wadiche,
Macroscopic and microscopic properties of a cloned glutamate transporter/chloride channel.
1998,
Pubmed
,
Xenbase
Watase,
Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice.
1998,
Pubmed
Watzke,
Early intermediates in the transport cycle of the neuronal excitatory amino acid carrier EAAC1.
2001,
Pubmed
Watzke,
The anion conductance of the glutamate transporter EAAC1 depends on the direction of glutamate transport.
2001,
Pubmed
Yernool,
Structure of a glutamate transporter homologue from Pyrococcus horikoshii.
2004,
Pubmed
Zerangue,
Flux coupling in a neuronal glutamate transporter.
1996,
Pubmed
,
Xenbase
