Editors' ChoiceSynaptic Transmission

Endocytotic Function for Syntaxin 1A

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Science's STKE  19 Sep 2006:
Vol. 2006, Issue 353, pp. tw322
DOI: 10.1126/stke.3532006tw322

Syntaxin 1A is a plasma membrane protein of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) family, well known for its essential roles in neuronal signaling in which it regulates trafficking, docking, and fusion of synaptic vesicles with the plasma membrane. Experiments from Yu et al. show that syntaxin 1A also has a role in internalization of vesicles containing a transporter for the neurotransmitter glutamate. Transport of glutamate is important to prevent excessive stimulation of glutamate receptors and to maintain the supply of glutamate for conversion to the inhibitory neurotransmitter GABA (γ-aminobutyric acid). Yu et al. showed that in rat C6 glioma cells, expression of transfected syntaxin 1A decreased glutamate transport and the abundance of the glutamate transporter EAAC1 (excitatory amino acid carrier 1) at the cell surface. Depletion of syntaxin 1A with small interference RNA increased the abundance of EEAC1 at the cell surface and increased glutamate transport. Excessive stimulation of cells with the glutamatergic agonist kainic acid (KA) reproduces effects seen in epilepsy. The authors tracked biotinylated EAAC1 in KA-treated cells and found that suppression of syntaxin 1A expression reduced KA-stimulated internalization of EAAC1 into an endosomal or lysosomal compartment. The results suggest, as the authors put it, that syntaxin 1A must now be considered to regulate "both the ‘ins’ and the ‘outs’ of synaptic neurotransmission."

Y.-X. Yu, L. Shen, P. Xia, Y.-W. Tang, L. Bao, G. Pei, Syntaxin 1A promotes the endocytic sorting of EAAC1 leading to inhibition of glutamate transport. J. Cell Sci. 119, 3776-3787 (2006). [Abstract] [Full Text]