Syntaxin-1 N-peptide and H abc -domain perform distinct essential functions in synaptic vesicle fusion

Peng Zhou, Zhiping P. Pang, Xiaofei Yang, Yingsha Zhang, Christian Rosenmund, Taulant Bacaj, Thomas C. Südhof

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


Among SNARE proteins mediating synaptic vesicle fusion, syntaxin-1 uniquely includes an N-terminal peptide ('N-peptide') that binds to Munc18-1, and a large, conserved H abc -domain that also binds to Munc18-1. Previous in vitro studies suggested that the syntaxin-1 N-peptide is functionally important, whereas the syntaxin-1 H abc -domain is not, but limited information is available about the in vivo functions of these syntaxin-1 domains. Using rescue experiments in cultured syntaxin-deficient neurons, we now show that the N-peptide and the H abc -domain of syntaxin-1 perform distinct and independent roles in synaptic vesicle fusion. Specifically, we found that the N-peptide is essential for vesicle fusion as such, whereas the H abc -domain regulates this fusion, in part by forming the closed syntaxin-1 conformation. Moreover, we observed that deletion of the H abc -domain but not deletion of the N-peptide caused a loss of Munc18-1 which results in a decrease in the readily releasable pool of vesicles at a synapse, suggesting that Munc18 binding to the H abc -domain stabilizes Munc18-1. Thus, the N-terminal syntaxin-1 domains mediate different functions in synaptic vesicle fusion, probably via formation of distinct Munc18/SNARE-protein complexes.

Original languageEnglish (US)
Pages (from-to)159-171
Number of pages13
JournalEMBO Journal
Issue number1
StatePublished - Jan 9 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


  • SM proteins
  • membrane fusion
  • neurotransmitter release
  • synapse
  • syntaxin


Dive into the research topics of 'Syntaxin-1 N-peptide and H abc -domain perform distinct essential functions in synaptic vesicle fusion'. Together they form a unique fingerprint.

Cite this