German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Department for NMR-based Structural Biology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Nat Struct Mol Biol. 2023 Jul;30(7):926-934. doi: 10.1038/s41594-023-01004-9. Epub 2023 May 22.
Synaptic vesicles are small membrane-enclosed organelles that store neurotransmitters at presynaptic terminals. The uniform morphology of synaptic vesicles is important for brain function, because it enables the storage of well-defined amounts of neurotransmitters and thus reliable synaptic transmission. Here, we show that the synaptic vesicle membrane protein synaptogyrin cooperates with the lipid phosphatidylserine to remodel the synaptic vesicle membrane. Using NMR spectroscopy, we determine the high-resolution structure of synaptogyrin and identify specific binding sites for phosphatidylserine. We further show that phosphatidylserine binding changes the transmembrane structure of synaptogyrin and is critical for membrane bending and the formation of small vesicles. Cooperative binding of phosphatidylserine to both a cytoplasmic and intravesicular lysine-arginine cluster in synaptogyrin is required for the formation of small vesicles. Together with other synaptic vesicle proteins, synaptogyrin thus can sculpt the membrane of synaptic vesicles.
突触小泡是一种小的膜包裹细胞器，在突触前末端储存神经递质。突触小泡的均匀形态对于大脑功能很重要，因为它能够储存定义良好的神经递质量，从而实现可靠的突触传递。在这里，我们表明突触小泡膜蛋白突触联蛋白与磷脂酰丝氨酸合作重塑突触小泡膜。我们使用 NMR 光谱学确定了突触联蛋白的高分辨率结构，并确定了磷脂酰丝氨酸的特定结合位点。我们进一步表明，磷脂酰丝氨酸结合改变了突触联蛋白的跨膜结构，对于膜弯曲和小泡的形成至关重要。磷脂酰丝氨酸与突触联蛋白细胞质和囊内赖氨酸-精氨酸簇的协同结合对于小泡的形成是必需的。与其他突触小泡蛋白一起，突触联蛋白因此可以塑造突触小泡的膜。
