Role of Habc domain in membrane trafficking and targeting of syntaxin 1A

Membrane syntaxin plays essential roles in exocytosis in eukaryotic cells. The conservative Habc domain in plasma membrane syntaxins implies important roles for syntaxin targeting and function. Our previous study showed Habc domain was necessary for the trafficking and cluster distribution of syntaxin 1A on the plasma membrane. Here we identified which of the three domains (Ha, Hb and Hc) was essential for Stx1A trafficking and clustering. We found that, in INS-1 cells, the mutant truncated with either Ha, Hb or Hc domain could be sorted to the cell surface by a different mechanism compared to that of whole Habc truncated mutant. In contrast to wild type Stx1A, none of the mutants showed cluster distribution at the functional sites, suggesting that the physiological localization of Stx1A relies on intact Habc domain. Furthermore Munc18-1 is found not to be essential for Stx1A cluster distribution, despite important role in stabilizing membrane delivery of Stx1A.