| Syntaxin 1A promotes the endocytic sorting of EAAC1 leading to inhibition of glutamate transport. | |
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MedLine Citation:
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PMID: 16959903 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The neuronal glutamate transporter, excitatory amino-acid carrier 1 (EAAC1), plays an important role in the modulation of neurotransmission and contributes to synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and to epileptogenesis. However, the mechanisms that regulate EAAC1 endocytic sorting and function remain largely unknown. Here, we first demonstrate that EAAC1 undergoes internalization through the clathrin-mediated pathway and further show that syntaxin 1A, a key molecule in synaptic exocytosis, potentiates EAAC1 internalization, thus leading to the functional inhibition of EAAC1. In the presence of the transmembrane domain of syntaxin 1A, its H3 coiled-coil domain of syntaxin 1A is necessary and sufficient for the inhibition of EAAC1. Furthermore, specific suppression of endogenous syntaxin 1A significantly blocked EAAC1 endocytic sorting and lysosomal degradation promoted by kainic acid, a drug for kindling the animal model of human temporal lobe epilepsy in rat, indicating a potential role of syntaxin 1A in epileptogenesis. These findings provide new evidence that syntaxin 1A serves as an intrinsic enhancer to EAAC1 endocytic sorting and further suggest that syntaxin 1A is conversant with both ;ins' and ;outs' of synaptic neurotransmission. |
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Authors:
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Yong-Xin Yu; Li Shen; Peng Xia; Ya-Wei Tang; Lan Bao; Gang Pei |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cell science Volume: 119 ISSN: 0021-9533 ISO Abbreviation: J. Cell. Sci. Publication Date: 2006 Sep |
Date Detail:
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Created Date: 2006-09-08 Completed Date: 2006-12-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0052457 Medline TA: J Cell Sci Country: England |
Other Details:
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Languages: eng Pagination: 3776-87 Citation Subset: IM |
Affiliation:
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Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Transport Systems
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drug effects,
metabolism* Animals Biological Transport Cells, Cultured Clathrin / metabolism Coated Pits, Cell-Membrane / drug effects, metabolism Endocytosis / drug effects, physiology* Endosomes / drug effects Excitatory Amino Acid Transporter 3 / genetics, metabolism* Gene Expression Regulation / drug effects Glutamates / metabolism* Humans Kainic Acid / pharmacology Lysosomes / drug effects Neurons / drug effects Protein Binding / drug effects Protein Structure, Tertiary RNA, Messenger / genetics, metabolism Rats Rats, Sprague-Dawley Syntaxin 1 / chemistry, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Transport Systems; 0/Clathrin; 0/Excitatory Amino Acid Transporter 3; 0/Glutamates; 0/RNA, Messenger; 0/Slc1a1 protein, rat; 0/Stx1a protein, rat; 0/Syntaxin 1; 487-79-6/Kainic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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