of calcium is sensed by synaptotagmin 1, which in turn dislodges complexin protein and allows the vesicle to fuse with the presynaptic membrane to release neurotransmitter. It has also been shown that the voltage-gated calcium channels directly interact with the t-SNAREs syntaxin 1A and SNAP-25, as well as with synaptotagmin 1. The interactions are able to inhibit calcium channel activity as well as tightly aggregate the molecules around the release site. There have been many clinical cases that link SNARE genes with neural disorders. Deficiency in SNAP-25 mRNA has been observed in hippocampal tissue of some schizophrenic patients, a SNAP-25 single-nucleotide polymorphism is linked to hyperactivity in autism-spectrum disorders, and overexpression of SNAP-25B leads to the early onset of bipolar disorder. Role in autophagy Macroautophagy is a catabolic process involving the formation of double-membrane bound organelles called autophagosomes, which aid in degradation of cellular components through fusion with lysosomes. During autophagy, portions of the cytoplasm are engulfed by a cup-shaped double-membrane structure called a phagophore and eventually become the contents of the fully assembled autophagosome. Autophagosome biogenesis requires the initiation and growth of phagophores, a process that was once thought to occur through de novo addition of lipids. However, recent evidence suggests that the lipids that contribute to the growing phagophores originate from numerous sources of membrane, including endoplasmic reticulum, Golgi, plasma membrane, and mitochondria. SNAREs play important roles in mediating vesicle fusion during phagophore initiation and expansion as well as autophagosome-lysosome fusion in the later stages of autophagy. Though the mechanism of phagophore initiation in mammals is unknown, SNAREs have been implicated in phagophore formation through homotypic fusion of small, clathrin-coated, single-membrane vesicles containing Atg16L, the v-SNARE VAMP7, and its partner t-SNAREs: Syntaxin-7, Syntaxin-8, and VTI1B. In yeast, the t-SNAREs Sec9p and Sso2p are required for exocytosis and promote tubulovesicular budding of Atg9 positive vesicles, which are also required for autophagosome biogenesis. Knocking out either of these SNAREs leads to accumulation of small Atg9 containing vesicles that do not fuse, therefore preventing the formation of the pre-autophagosomal structure. In addition to phagophore assembly, SNAREs are also important in mediating autophagosome-lysosome fusion. In mammals, the SNAREs VAMP7, VAMP8, and VTI1B are required in autophagosome-lysosome fusion and this process is impaired in lysosomal storage disorders where cholesterol accumulates in the lysosome and sequesters SNAREs in cholesterol rich regions of the membrane preventing their recycling. Recently, syntaxin 17 (STX17) was identified as