Alix is required for activity-dependent bulk endocytosis at brain synapses

• DOI: 10.1371/journal.pbio.3001659
• Publication Date: 2022-06-03T17:57:08Z
• Authors: Marine H. Laporte; Kwang Il Chi; Laura C. Caudal; Na Zhao; Yvonne Schwarz; Marta Rolland; José Martinez-Her...; Magalie Martineau; Christine Chatellard; Eric Denarier; Vincent Mercier; Florent Lemaître; Béatrice Blot; Eve Moutaux; Maxime Cazorla; David Perrais; Fabien Lanté; Dieter Bruns; Sandrine Fraboulet; Fiona J. Hemming; Frank Kirchhoff; Rémy Sadoul
• Keywords: Synaptic vesicle recycling; Bulk endocytosis

In chemical synapses undergoing high frequency stimulation, vesicle components can be retrieved from the plasma membrane via a clathrin-independent process called activity-dependent bulk endocytosis (ADBE). Alix (ALG-2-interacting protein X/PDCD6IP) is an adaptor binding to ESCRT and endophilin-A proteins which required for in fibroblasts. expressed neurons concentrates at during epileptic seizures. Here, we used cultured show that recruited presynapses where it interacts with conditions triggering ADBE. Using knockout (ko) neurons, showed this recruitment, requires interaction calcium-binding ALG-2, necessary We also found presynaptic compartments of ko hippocampi display subtle morphological defects compatible flawed synaptic activity plasticity detected electrophysiologically. Furthermore, mice lacking forebrain undergo less seizures kainate-induced status epilepticus reduced propagation epileptiform activity. These results thus impairment ADBE due lack neuronal leads abnormal recovery physiological or pathological repeated stimulations.