Phospholipid Scramblase-1 controls efficient neurotransmission and synaptic vesicle retrieval at cerebellar synapses.
Fiche publication
Date publication
juin 2024
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GASMAN Stéphane, Dr CHASSEROT-GOLAZ Sylvette, Mme ROYER Cathy, Dr VITALE Nicolas, Dr TOTH Petra, Dr ORY Stéphane
Tous les auteurs :
Caputo M, Ivanova D, Chasserot-Golaz S, Doussau F, Haeberlé AM, Royer C, Ozkan S, Ecard J, Vitale N, Cousin MA, Tóth P, Gasman S, Ory S
Lien Pubmed
Résumé
Phospholipids 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 phospholipid 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 synapses and both PS egress and synaptic vesicle endocytosis are inhibited in cultured neurons from male and female mice, demonstrating that PLSCR1 controls phospholipid asymmetry remodeling and synaptic vesicle retrieval following neurotransmitter release. Altogether, our data reveal a novel key role for PLSCR1 in synaptic vesicle recycling and provide the first evidence that phospholipid scrambling at the plasma membrane is a prerequisite for optimal presynaptic performance. During calcium-regulated exocytosis, phospholipids like phosphatidylserine (PS) undergo dynamic remodeling. Phospholipid Scramblase-1 (PLSCR1) belongs to a family of proteins able to randomize lipids at the cell surface in response to intracellular Ca increases. Whether PLSCR1 and PS egress have a role during neurotransmission is unknown. We show that PLSCR1 expression is restricted to specific brain regions capable of sustaining neurotransmission during high firing rates. In the absence of PLSCR1, synaptic transmission is impaired, and both PS egress and synaptic vesicle endocytosis are hindered. This study highlights the pivotal role of PLSCR1 in regulating optimal presynaptic performance by redistributing phospholipid at the plasma membrane to control compensatory endocytosis.
Référence
J Neurosci. 2024 06 5;: