AI Summary
This article focuses on the role of phospholipid scramblase 1 (PLSCR1) in neurotransmission at cerebellar synapses. PLSCR1 is responsible for reshuffling phospholipids in the plasma membrane in response to calcium activation. The study found that PLSCR1 is expressed in cerebellar granule cells and plays a crucial role in phosphatidylserine egress and synaptic vesicle retrieval. Synaptic transmission was impaired in mice lacking PLSCR1, indicating its importance in maintaining lipid asymmetry and synapse function. The research highlights the significance of PLSCR1 in synaptic vesicle recycling and suggests that lipid scrambling is essential for optimal presynaptic performance.
Phospholipids (PLs) are asymmetrically distributed at the plasma membrane. This asymmetric lipid distribution is transiently altered during calcium-regulated exocytosis, but the impact of this transient remodeling on presynaptic function is currently unknown. As phospholipid scramblase 1 (PLSCR1) randomizes PL distribution between the two leaflets of the plasma membrane in response to calcium activation, we set out to determine its role in neurotransmission. We report here that PLSCR1 is expressed in cerebellar granule cells (GrCs) and that PLSCR1-dependent phosphatidylserine egress occurred at synapses in response to neuron stimulation. Synaptic transmission is impaired at GrC Plscr1–/– synapses, and both PS egress and synaptic vesicle (SV) endocytosis are inhibited in Plscr1–/– cultured neurons from male and female mice, demonstrating that PLSCR1 controls PL asymmetry remodeling and SV retrieval following neurotransmitter release. Altogether, our data reveal a novel key role for PLSCR1 in SV recycling and provide the first evidence that PL scrambling at the plasma membrane is a prerequisite for optimal presynaptic performance.