Syntaxin 1A promotes the endocytic sorting of EAAC1 leading to inhibition of glutamate transport
| Autor: | Lan Bao, Gang Pei, Yongxin Yu, Peng Xia, Li Shen, Ya-Wei Tang |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Amino Acid Transport Systems
Endosome media_common.quotation_subject Endocytic cycle Excitatory Amino Acid Transporter 3 Syntaxin 1 Endosomes Neurotransmission Biology Rats Sprague-Dawley Glutamates Animals Humans RNA Messenger Internalization Cells Cultured media_common Neurons Kainic Acid Glutamate receptor Biological Transport Coated Pits Cell-Membrane Cell Biology Clathrin Endocytosis Syntaxin 3 Protein Structure Tertiary Rats Cell biology Gene Expression Regulation nervous system Lysosomes Protein Binding |
| Zdroj: | Journal of Cell Science. 119:3776-3787 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.03151 |
| Popis: | 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 γ-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. |
| Databáze: | OpenAIRE |
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