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Functional modulation of the glutamate transporter variant GLT1b by the PDZ domain protein PICK1.
Sogaard R
,
Borre L
,
Braunstein TH
,
Madsen KL
,
MacAulay N
.
Abstract
The dominant glutamate transporter isoform in the mammalian brain, GLT1, exists as at least three splice variants, GLT1a, GLT1b, and GLT1c. GLT1b interacts with the scaffold protein PICK1 (protein interacting with kinase C1), which is implicated in glutamatergic neurotransmission via its regulatory effect on trafficking of AMPA-type glutamate receptors. The 11 extreme C-terminal residues specific for the GLT1b variant are essential for its specific interaction with the PICK1 PDZ domain, but a functional consequence of this interaction has remained unresolved. To identify a functional effect of PICK1 on GLT1a or GLT1b separately, we employed the Xenopus laevis expression system. GLT1a and GLT1b displayed similar electrophysiological properties and EC50 for glutamate. Co-expressed PICK1 localized efficiently to the plasma membrane and resulted in a 5-fold enhancement of the leak current in GLT1b-expressing oocytes with only a minor effect on [(3)H]glutamate uptake. Three different GLT1 substrates all caused a slow TBOA-sensitive decay in the membrane current upon prolonged application, which provides support for the leak current being mediated by GLT1b itself. Leak and glutamate-evoked currents in GLT1a-expressing oocytes were unaffected by PICK1 co-expression. PKC activation down-regulated GLT1a and GLT1b activity to a similar extent, which was not affected by co-expression of PICK1. In conclusion, PICK1 may not only affect glutamatergic neurotransmission by its regulatory effect on glutamate receptors but may also affect neuronal excitability via an increased GLT1b-mediated leak current. This may be particularly relevant in pathological conditions such as amyotrophic lateral sclerosis and cerebral hypoxia, which are associated with neuronal GLT1b up-regulation.
Arriza,
Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex.
1994, Pubmed,
Xenbase
Arriza,
Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex.
1994,
Pubmed
,
Xenbase
Baron,
Protein kinase C stimulates the acid-sensing ion channel ASIC2a via the PDZ domain-containing protein PICK1.
2002,
Pubmed
Bassan,
Interaction between the glutamate transporter GLT1b and the synaptic PDZ domain protein PICK1.
2008,
Pubmed
Bergles,
Comparison of coupled and uncoupled currents during glutamate uptake by GLT-1 transporters.
2002,
Pubmed
Billups,
Modulation of non-vesicular glutamate release by pH.
1996,
Pubmed
Borre,
Arginine 445 controls the coupling between glutamate and cations in the neuronal transporter EAAC-1.
2004,
Pubmed
Chen,
Expression of a variant form of the glutamate transporter GLT1 in neuronal cultures and in neurons and astrocytes in the rat brain.
2002,
Pubmed
Chen,
The glutamate transporters EAAT2 and EAAT3 mediate cysteine uptake in cortical neuron cultures.
2003,
Pubmed
Chen,
The glutamate transporter GLT1a is expressed in excitatory axon terminals of mature hippocampal neurons.
2004,
Pubmed
D'Amico,
The surface density of the glutamate transporter EAAC1 is controlled by interactions with PDZK1 and AP2 adaptor complexes.
2010,
Pubmed
Danbolt,
Localization of transporters using transporter-specific antibodies.
1998,
Pubmed
Danbolt,
Glutamate uptake.
2001,
Pubmed
Dev,
PICK1 interacts with and regulates PKC phosphorylation of mGLUR7.
2000,
Pubmed
Focant,
PICK1 expression in reactive astrocytes within the spinal cord of amyotrophic lateral sclerosis (ALS) rats.
2013,
Pubmed
Gebhardt,
Exon-skipping splice variants of excitatory amino acid transporter-2 (EAAT2) form heteromeric complexes with full-length EAAT2.
2010,
Pubmed
González-González,
The glutamate transporter GLT1b interacts with the scaffold protein PSD-95.
2008,
Pubmed
González-González,
PKC-dependent endocytosis of the GLT1 glutamate transporter depends on ubiquitylation of lysines located in a C-terminal cluster.
2008,
Pubmed
Grewer,
Electrogenic glutamate transporters in the CNS: molecular mechanism, pre-steady-state kinetics, and their impact on synaptic signaling.
2005,
Pubmed
Guillet,
Differential regulation by protein kinases of activity and cell surface expression of glutamate transporters in neuron-enriched cultures.
2005,
Pubmed
Holmseth,
The concentrations and distributions of three C-terminal variants of the GLT1 (EAAT2; slc1a2) glutamate transporter protein in rat brain tissue suggest differential regulation.
2009,
Pubmed
Ingram,
Dopamine transporter-mediated conductances increase excitability of midbrain dopamine neurons.
2002,
Pubmed
Jackson,
Modulation of the neuronal glutamate transporter EAAT4 by two interacting proteins.
2001,
Pubmed
Jansen,
PICK1 expression in the Drosophila central nervous system primarily occurs in the neuroendocrine system.
2009,
Pubmed
Jespersen,
Dual-function vector for protein expression in both mammalian cells and Xenopus laevis oocytes.
2002,
Pubmed
,
Xenbase
Kalandadze,
Protein kinase C activation decreases cell surface expression of the GLT-1 subtype of glutamate transporter. Requirement of a carboxyl-terminal domain and partial dependence on serine 486.
2002,
Pubmed
Kanai,
Electrogenic properties of the epithelial and neuronal high affinity glutamate transporter.
1995,
Pubmed
,
Xenbase
Karatas-Wulf,
Protein kinase C-dependent trafficking of glutamate transporters excitatory amino acid carrier 1 and glutamate transporter 1b in cultured cerebellar granule cells.
2009,
Pubmed
Kim,
Interaction of the AMPA receptor subunit GluR2/3 with PDZ domains regulates hippocampal long-term depression.
2001,
Pubmed
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
Madsen,
Membrane localization is critical for activation of the PICK1 BAR domain.
2008,
Pubmed
Maragakis,
Altered expression of the glutamate transporter EAAT2b in neurological disease.
2004,
Pubmed
Moeller,
Role of multiple phosphorylation sites in the COOH-terminal tail of aquaporin-2 for water transport: evidence against channel gating.
2009,
Pubmed
,
Xenbase
Nourry,
PDZ domain proteins: plug and play!
2003,
Pubmed
Otis,
Anion currents and predicted glutamate flux through a neuronal glutamate transporter.
1998,
Pubmed
Otis,
Isolation of current components and partial reaction cycles in the glial glutamate transporter EAAT2.
2000,
Pubmed
Pow,
Loss of glial glutamate transporters and induction of neuronal expression of GLT-1B in the hypoxic neonatal pig brain.
2004,
Pubmed
Rauen,
A new GLT1 splice variant: cloning and immunolocalization of GLT1c in the mammalian retina and brain.
2004,
Pubmed
Rothstein,
Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate.
1996,
Pubmed
Schmitt,
A splice variant of glutamate transporter GLT1/EAAT2 expressed in neurons: cloning and localization in rat nervous system.
2002,
Pubmed
Sheldon,
The role of glutamate transporters in neurodegenerative diseases and potential opportunities for intervention.
2007,
Pubmed
Shigeri,
Effects of threo-beta-hydroxyaspartate derivatives on excitatory amino acid transporters (EAAT4 and EAAT5).
2001,
Pubmed
,
Xenbase
Shimamoto,
DL-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters.
1998,
Pubmed
,
Xenbase
Staudinger,
PICK1: a perinuclear binding protein and substrate for protein kinase C isolated by the yeast two-hybrid system.
1995,
Pubmed
Steinberg,
Targeted in vivo mutations of the AMPA receptor subunit GluR2 and its interacting protein PICK1 eliminate cerebellar long-term depression.
2006,
Pubmed
Sullivan,
Cloning, transport properties, and differential localization of two splice variants of GLT-1 in the rat CNS: implications for CNS glutamate homeostasis.
2004,
Pubmed
Susarla,
Internalization and degradation of the glutamate transporter GLT-1 in response to phorbol ester.
2008,
Pubmed
Søgaard,
Elevated ammonium levels: differential acute effects on three glutamate transporter isoforms.
2012,
Pubmed
,
Xenbase
Torres,
Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1.
2001,
Pubmed
Vandenberg,
Constitutive ion fluxes and substrate binding domains of human glutamate transporters.
1995,
Pubmed
,
Xenbase
Volk,
Developmental regulation of protein interacting with C kinase 1 (PICK1) function in hippocampal synaptic plasticity and learning.
2011,
Pubmed
Wadiche,
Ion fluxes associated with excitatory amino acid transport.
1995,
Pubmed
,
Xenbase
Watzke,
The anion conductance of the glutamate transporter EAAC1 depends on the direction of glutamate transport.
2001,
Pubmed
Xia,
Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1.
1999,
Pubmed
Zerangue,
Flux coupling in a neuronal glutamate transporter.
1996,
Pubmed
,
Xenbase
Zhou,
Glutamate transporter cluster formation in astrocytic processes regulates glutamate uptake activity.
2004,
Pubmed
