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Pré-Publication, Document De Travail Année : 2020

ALG-2 interacting protein-X (Alix) is required for activity-dependent bulk endocytosis at brain synapses

Eric Denarier
Frank Kirchhoff
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Rémy Sadoul
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Résumé

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 protein binding to ESCRT and endophilin-A proteins and thereby driving deformation and fission of endosomal and cell surface membranes. In fibroblasts, Alix is required for clathrin-independent endocytosis. Here, using electron microscopy, we show that synapses from mice lacking Alix have subtle defects in presynaptic compartments, translating into flawed short-term synaptic plasticity. Using cultured neurons, we demonstrate that Alix is specifically involved in ADBE. We further demonstrate that in order to perform ADBE, Alix must be recruited to synapses by the calcium binding protein ALG-2 and interact with endophilin-A. Finally, we show that Alix ko mice are resistant to kainaite-induced epileptic seizures. These results thus highlight Alix ko mice as an invaluable model to study the exact role of ADBE at synapses undergoing physiological or pathological stimulations.
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Dates et versions

hal-03039230 , version 1 (03-12-2020)

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Marine H Laporte, Kwang Il Chi, Marta Rolland, Laura C Caudal, José Martinez-Hernandez, et al.. ALG-2 interacting protein-X (Alix) is required for activity-dependent bulk endocytosis at brain synapses. 2020. ⟨hal-03039230⟩
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