Membrane Transport, Structure, Function, and Biogenesis
Domain Requirement for the Membrane Trafficking and Targeting of Syntaxin 1A*

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Syntaxin plays a key role in intracellular membrane fusion in eukaryotic cells. The function of syntaxin relies on its proper trafficking to and targeting at the target membrane. The mechanisms underlying the trafficking and targeting of syntaxin to its physiological sites remain poorly understood. Here we have analyzed the trafficking of syntaxin 1A in INS-1 and CHO cells. We have identified the transmembrane domain together with several flanking positive-charged amino acids as the minimal domain required for the membrane delivery. Interestingly, we found that SNARE motif-exposed syntaxin 1A mutants were retained in endoplasmic reticulum (ER) and failed to transport to the cell surface in the absence of SNAP-25, suggesting that the exposure of the SNARE motif causes ER retention and complexation with SNAP-25 helps the ER escape. Finally, our data propose two key roles for the Habc domain: to protect nonspecific interaction by masking the SNARE motif and to participate in the clustering of syntaxin 1A to the fusion sites in the plasma membrane.

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This work was supported by National Science Foundation of China Grants 30025023, 30270363, 30130230, and 30500114, the Chinese Academy of Science Project (KSCX2-SW-224, Y2004018), and National Basic Research Program of China (973) Grant 2004CB720000 (to T. X.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1

These authors contribute equally to the work.