STX17 Human

Syntaxin-17 is unique among syntaxins due to its long C-terminal hydrophobic domain (CHD), which consists of 44 amino acids containing two hydrophobic segments separated by a lysine residue . This structure is essential for its function in membrane fusion. The protein also has a basic amino acid-enriched C-terminal tail, which is crucial for its recruitment to mature autophagosomes .

During autophagy, cytoplasmic constituents are engulfed by autophagosomes, which then fuse with lysosomes to degrade their contents. Syntaxin-17 is recruited to mature autophagosomes, a process regulated by the accumulation of phosphatidylinositol 4-phosphate (PI4P) in the autophagosomal membrane . This recruitment is essential for the fusion of autophagosomes with lysosomes, ensuring the degradation of the enclosed contents .

Syntaxin-17 is one of the six ancient eukaryotic Qa-SNAREs, but it has been lost in multiple lineages during evolution, including yeast . Despite its ancient origins, Syntaxin-17 has conserved roles across different organisms. For instance, in mammals, it is involved in mitochondrial division, autophagosome formation, and lipid droplet expansion . However, its functions can vary; for example, in flies, it primarily mediates autophagy, while in nematodes, it facilitates mitochondrial division .

Mutations or dysregulation of Syntaxin-17 have been associated with various diseases, including Amyotrophic Lateral Sclerosis Type 22 and Alopecia Universalis Congenita . Understanding the function and regulation of Syntaxin-17 is therefore crucial for developing therapeutic strategies for these conditions.