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J. Cell Sci. 119 (18): 3776-3787

Research Article

Syntaxin 1A promotes the endocytic sorting of EAAC1 leading to inhibition of glutamate transport

Yong-Xin Yu1,2, Li Shen1, Peng Xia1, Ya-Wei Tang1, Lan Bao1,*, and Gang Pei1,*

1 Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences
2 Graduate School of Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, People's Republic of China

* Authors for correspondence (e-mail: baolan{at}; gpei{at}

Accepted for publication 22 June 2006.

Abstract: 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.

Key Words: EAAC1 • Syntaxin 1A • Endocytic sorting • Glutamate transport • Kainic acid • Surface expression

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