Alix is required for activity-dependent bulk endocytosis at brain synapses - Groupe Entrée et bourgeonnement des virus à enveloppe / Entry and Budding of Enveloped Viruses Group (EBEV) Access content directly
Journal Articles PLoS Biology Year : 2022

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

Kwang Il Chi
Laura Caudal
Na Zhao
Eric Denarier
Frank Kirchhoff

Abstract

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 which is required for clathrin-independent endocytosis in fibroblasts. Alix is expressed in neurons and concentrates at synapses during epileptic seizures. Here, we used cultured neurons to show that Alix is recruited to presynapses where it interacts with and concentrates endophilin-A during conditions triggering ADBE. Using Alix knockout (ko) neurons, we showed that this recruitment, which requires interaction with the calcium-binding protein ALG-2, is necessary for ADBE. We also found that presynaptic compartments of Alix ko hippocampi display subtle morphological defects compatible with flawed synaptic activity and plasticity detected electrophysiologically. Furthermore, mice lacking Alix in the forebrain undergo less seizures during kainate-induced status epilepticus and reduced propagation of the epileptiform activity. These results thus show that impairment of ADBE due to the lack of neuronal Alix leads to abnormal synaptic recovery during physiological or pathological repeated stimulations.
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Dates and versions

hal-03876511 , version 1 (28-11-2022)

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Marine Laporte, Kwang Il Chi, Laura Caudal, Na Zhao, Yvonne Schwarz, et al.. Alix is required for activity-dependent bulk endocytosis at brain synapses. PLoS Biology, 2022, 20 (6), pp.e3001659. ⟨10.1371/journal.pbio.3001659⟩. ⟨hal-03876511⟩
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