ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002
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.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 90 citations in OpenAlex.
- Article
- Rapid Regulation of Glutamate Transport: Where Do We Go from Here?Neurochemical research · 2022Review
- Regulation of Glutamate, GABA and Dopamine Transporter Uptake, Surface Mobility and Expression.Frontiers in cellular neuroscience · 2021Review
- Constitutive Endocytosis of the Neuronal Glutamate Transporter Excitatory Amino Acid Transporter-3 Requires ARFGAP1.Frontiers in physiology · 2021Article
- The cellular mechanisms that maintain neuronal polarity.Nature reviews. Neuroscience · 2016Review
- The importance of the excitatory amino acid transporter 3 (EAAT3).Neurochemistry international · 2016Review
- Neuronal ClC-3 Splice Variants Differ in Subcellular Localizations, but Mediate Identical Transport Functions.The Journal of biological chemistry · 2015Article
- Differential regulation of two isoforms of the glial glutamate transporter EAAT2 by DLG1 and CaMKII.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- The transmembrane transporter domain of glutamate transporters is a process tip localizer.Scientific reports · 2015Article
- Melanocortin 3 receptor has a 5' exon that directs translation of apically localized protein from the second in-frame ATG.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Glutamate as a neurotransmitter in the healthy brain.Journal of neural transmission (Vienna, Austria : 1996) · 2014Review
- Article
- Apical targeting of the P2Y(4) receptor is directed by hydrophobic and basic residues in the cytoplasmic tail.American journal of physiology. Cell physiology · 2013Article
- Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation.ASN neuro · 2012Review
- The density of EAAC1 (EAAT3) glutamate transporters expressed by neurons in the mammalian CNS.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Hetero-oligomerization of neuronal glutamate transporters.The Journal of biological chemistry · 2011Article
- mRNA for the EAAC1 subtype of glutamate transporter is present in neuronal dendrites in vitro and dramatically increases in vivo after a seizure.Neurochemistry international · 2011Article
- Regulation of glial glutamate transporters by C-terminal domains.The Journal of biological chemistry · 2011Article
- Myosin-dependent targeting of transmembrane proteins to neuronal dendrites.Nature neuroscience · 2009Article
- Disease-causing dysfunctions of barttin in Bartter syndrome type IV.Journal of the American Society of Nephrology : JASN · 2009Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The glutamate transporter excitatory amino acid transporter 3 (EAAT3) is polarized to the apical surface in epithelial cells and localized to the dendritic compartment in hippocampal neurons, where it is clustered adjacent to postsynaptic sites. In this study, we analyzed the sequences in EAAT3 that are responsible for its polarized localization in Madin-Darby canine kidney (MDCK) cells and neurons. Confocal microscopy and cell surface biotinylation assays demonstrated that deletion of the EAAT3 C terminus or replacement of the C terminus of EAAT3 with the analogous region in EAAT1 eliminated apical localization in MDCK cells. The C terminus of EAAT3 was sufficient to redirect the basolateral-preferring EAAT1 and the nonpolarized EAAT2 to the apical surface. Using alanine substitution mutants, we identified a short peptide motif in the cytoplasmic C-terminal region of EAAT3 that directs its apical localization in MDCK cells. Mutation of this sequence also impairs dendritic targeting of EAAT3 in hippocampal neurons but does not interfere with the clustering of EAAT3 on dendritic spines and filopodia. These data provide the first evidence that an identical cytoplasmic motif can direct apical targeting in epithelia and somatodendritic targeting in neurons. Moreover, our results demonstrate that the two fundamental features of the localization of EAAT3 in neurons, its restriction to the somatodendritic domain and its clustering near postsynaptic sites, are mediated by distinct molecular mechanisms.
Indexed as
Identifiers
12486157PMC6758410W2140166756What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.