The syntaxins

Abstract

The SNARE hypothesis predicts that a family of SNAP receptors are localized to and function in diverse intracellular membrane compartments where membrane fusion processes take place. Syntaxins, the prototype family of SNARE proteins, have a carboxy-terminal tail-anchor and multiple coiled-coil domains. There are 15 members of the syntaxin family in the human genome and 7 syntaxin-like genes in the yeast Saccharomyces cerevisiae. In conjunction with other SNAREs and with the cytoplasmic NSF and SNAP proteins, syntaxins mediate vesicle fusion in diverse vesicular transport processes along the exocytic and the endocytic pathway. They are crucial components that both drive and provide specificity to the myriad vesicular fusion processes that characterize the eukaryotic cell.

Figure 1

A nearest-neighbor dendrogram of the 7 S. cerevisiae and 15 mammalian syntaxins, generated with the DNASTAR program. See Table 2 for yeast gene names; syn, syntaxin. There are also several syntaxin-like genes in the Drosophila and C. elegans genome; see Bock et al. [6] for a more extensive phylogenetic analysis that includes these sequences.

Figure 2

The structure of syntaxin and a syntaxin-containing SNARE complex. (a) A graphical output of the analysis with the COILS program [16] of syntaxin 1A, for potential coiled-coil-forming regions. A window size of 21 residues was used. (b) Schematic representation of the structure of syntaxin 1A, illustrating both the linear domain arrangement (upper diagram) and the coiled-coil domains (blue) with spatial relevance to one another (lower diagram). N, amino terminus; C, carboxyl terminus. (c) Schematic representation of the four-helical bundle structure of the core fusion complex formed by syntaxin 1A (blue), synaptobrevin/VAMP (red) and SNAP-25 (green) at the presynaptic plasma membrane.

Figure 3

Subcellular localization of syntaxins (red) in a mammalian cell relative to the various membrane-bound compartments, anterograde and endocytotic/retrograde flow of traffic (green and purple arrows, respectively) and known membrane-transport steps (black). EE, early endosome; ERGIC, ER-Golgi intermediate compartment; Glut4, a glucose transporter molecule; LE, late endosome; RE, recycling endosome, SER, smooth ER; syn, syntaxin; TGN, trans-Golgi network.