Phosphatidylserine-dependent structure of synaptogyrin remodels the synaptic vesicle membrane

Abstract

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.

An adjustable multistage resistance switching behavior of a photoelectric artificial synaptic device with a ferroelectric diode effect for neuromorphic computing

“…24 The presynaptic membrane becomes more permeable to Ca 2+ when nerve impulses are passed from axons to synaptosomes, and Ca 2+ from the synaptic gap enters the synaptosomes, encouraging a tight fusion of the presynaptic membrane and synaptic vesicles. 13,25,26 Vesicular transmitters are released into the synaptic gap where they diffuse to bind to protein receptors on the postsynaptic membrane. Excitatory postsynaptic current (EPSC) is the result of this action, which also changes the permeability of the postsynaptic membrane.…”

“…These neurotransmitters traverse the synaptic gap and bind to the receptors located on the postsynaptic neuron, leading to the generation of a postsynaptic current (PSC). 26,33,34 The synaptic weight, which is interpreted as the strength of the connection between two neurons, is reflected by the value of PSC. The strength of the connection between two neurons is determined by the synaptic weight, which can be increased or decreased.…”

Periodic heat waves-induced neuronal etiology in the elderly is mediated by gut-liver-brain axis: a transcriptome profiling approach

“…This may act as a pro-inflammatory mediator that can activate cells such as astrocytes and microglia, potentially leading to sustained inflammation, neuronal damage, and cognitive impairment in neuroinflammatory pathology 51,52 . Additionally, downregulation of the Interleukin-12 (IL-12) signaling has been observed in heat stress-induced neuronal pathways; IL-12 is associated with inducing neuroprotection and shaping the trophic factor milieu within the inflamed central nervous system, with neurons being the dominant source of trophic factors 53 www.nature.com/scientificreports/ 4 which is novel in depicting neuronal distress while other proteins of the same family were previously correlated with synaptic plasticity factors under various neurological disease pathology 54,55 . Serpine 3, was inhibited in heat-stressed brain tissues and is known to hasten the neuronal apoptosis and more severe impairments of spatial learning and memory following a hippocampal injury 56 .…”

Interplay between Copper, Phosphatidylserine, and α-Synuclein Suggests a Link between Copper Homeostasis and Synaptic Vesicle Cycling

“…Nevertheless, such lipid asymmetry would be broken in neurotransmission. During vesicle fusion, phospholipid scramblase-1 is expected to randomize the lipid distribution; while during vesicle recycling, two PS lipids, one from the inner leaflet and the other from the outer leaflet, are required to cooperatively bind to both cytoplasmic and intravesicular lysine–arginine clusters in synaptogyrin for the formation of small vesicles . Therefore, regardless of the exact nature of asymmetry in PS lipid distribution in synaptic vesicle before neurotransmission, Cu 2+ ions would be able to interact with PS transiently during the process of synaptic vesicle release and recycling.…”