Sphingomyelinase modulates synaptic vesicle mobilization at the mice neuromuscular junctions

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• Sphingomyelin is crucial for presynaptic membrane structure and lipid raft organization.
• Hydrolysis of sphingomyelin by secretory sphingomyelinases (SMases) occurs in pathological conditions.
• Understanding SMase effects on neurotransmission is vital for neurological research.

Purpose of the Study:

• To investigate the impact of SMase on exocytotic neurotransmitter release at mouse diaphragm neuromuscular junctions.
• To elucidate the role of SMase in synaptic membrane dynamics and vesicle fusion.
• To differentiate the effects of SMase on plasma versus vesicular membranes.

Main Methods:

• Utilized microelectrode recordings to measure postsynaptic potentials.
• Employed styryl (FM) dyes to assess neuromuscular transmission and synaptic vesicle dynamics.
• Assessed membrane properties using fluorescent techniques.

Main Results:

• Low-concentration SMase disrupted synaptic membrane lipid packing.
• SMase enhanced neurotransmitter release and FM-dye unloading at high stimulation frequencies (10-70 Hz).
• SMase prevented the shift from full-collapse fusion to kiss-and-run exocytosis during high-frequency activity, but inhibited transmission when acting on vesicles.

Conclusions:

• Hydrolysis of plasma membrane sphingomyelin by SMase facilitates synaptic vesicle mobilization and promotes full fusion exocytosis.
• SMase acting on vesicular membranes exerts a depressant effect on neurotransmission.
• Changes in synaptic membrane properties and intracellular signaling partially mediate SMase effects.