8.A.91 The Syntaxin (Syntaxin) Family
Syntaxins, Syxs, play roles in hormone and neurotransmitter exocytosis and are potentially involved in docking of synaptic vesicles at presynaptic active zones. During exocytosis, vesicle-associated v-SNARE (synaptobrevin) and target cell-associated t-SNAREs (syntaxin and SNAP-25) assemble into a core trans-SNARE complex. This complex plays a versatile role at various stages of exocytosis ranging from the priming to fusion pore formation and expansion, finally resulting in the release or exchange of the vesicle content (Han et al. 2017). Syntaxins may also mediate Ca2+-regulation of exocytosis in the acrosomal reaction in sperm (Hutt et al. 2005). SNARE proteins (synaptobrevin, SNAP25 and syntaxin), synaptophysin, Ca2+/calmodulin, and members of the synaptotagmin protein family (Syt1, Syt4, Syt7 and Syt11) are involved in the balance and tight coupling of exo-endocytosis in neurons (Xie et al. 2017). Syntaxins regulate many channels and carriers including those listed in TCDB under TC#s 1.A.1.11.3, 1.A.1.11.4, 1.A.1.11.8, 1.A.1.2.13, 1.A.6.1.1 and 2.A.22.1.4 (see these entries) (Saxena et al. 2006). Some syntaxins are listed under family 1.F.1 (see 1.F.1.1.3 and 1.F.1.1.4). Syntaxin 5 (Stx5) in mammals and its ortholog Sed5p in Saccharomyces cerevisiae mediate anterograde and retrograde endoplasmic reticulum (ER)-Golgi trafficking. The TMSs of syntaxin line the fusion pore of Ca2+-triggered exocytosis, and the fusion pore is formed at least in part by a circular arrangement of 5 to 8 Syx TMSs in the plasma membrane (Han et al. 2004).
Syntaxin5, human Stx5 (TC# 8.A.91.1.9) and yeast Sed5p (TC# 8.A.91.1.10), are structurally conserved and are both regulated by interactions with other ER-Golgi SNARE proteins, the Sec1/Munc18-like protein Scfd1/Sly1p and the membrane tethering complexes COG, p115, and GM130. Despite these similarities, yeast Sed5p and mammalian Stx5 are differently recruited to COPII-coated vesicles, and Stx5 interacts with the microtubular cytoskeleton, whereas Sed5p does not. Possibly these different Stx5 interactions contribute to structural differences in ER-Golgi transport between mammalian and yeast cells (Linders et al. 2019).