ALG-2 interacting protein-X (Alix) is required for activity-dependent bulk endocytosis at brain synapses
Laporte, M. H.; Chi, K. I.; Rolland, M.; Caudal, L. C.; Martinez-Hernandez, J.; Martineau, M.; Chatellard, C.; Denarier, E.; Mercier, V.; Lemaitre, F.; Blot, B.; Moutaux, E.; Cazorla, M.; Buisson, A.; Perrais, D.; Fraboulet, S.; Lante, F.; Kirchhoff, F.; Hemming, F. J.; Sadoul, R.
Show 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 ABDE. 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 alters synaptic recovery during physiological or pathological repeated stimulations.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Endophilin A1 facilitates organization of the GABAergic postsynaptic machinery to maintain excitation-inhibition balance 98%
- Endosomal sorting protein SNX4 limits synaptic vesicle docking and release 98%
- GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals 97%
Similar papers in this journal
- Bassoon controls synaptic vesicle pools via regulation of presynaptic phosphorylation and cAMP homeostasis 97%
- Microglia shape hippocampal networks but are dispensable for pruning of synapses during development 97%
- Carbonic anhydrase VII regulates dendritic spine morphology and density via actin filament bundling 96%
Similar papers in this journal
- Prolonged activity-deprivation causes pre- and postsynaptic compensatory plasticity at neocortical excitatory synapses 96%
- The synapsin-dependent vesicle cluster is crucial for presynaptic plasticity at a glutamatergic synapse in male mice 96%
- Progressive circuit hyperexcitability in mouse neocortical slice cultures with increasing duration of activity silencing 96%
Similar papers in this journal
- Abnormal AMPAR-mediated synaptic plasticity, cognitive and autistic-like behaviors in a missense Fmr1 mutant mouse model of Fragile X syndrome 96%
- A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation 95%
- Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to 1 CA1 by differential modulation of feedforward inhibitory circuits 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.