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doi:10.22028/D291-37079
Titel: | Alix is required for activity-dependent bulk endocytosis at brain synapses |
VerfasserIn: | Laporte, Marine H. Chi, Kwang I.l. Caudal, Laura C. Zhao, Na Schwarz, Yvonne Rolland, Marta Martinez-Hernandez, José Martineau, Magalie Chatellard, Christine Denarier, Eric Mercier, Vincent Lemaître, Florent Blot, Béatrice Moutaux, Eve Cazorla, Maxime Perrais, David Lanté, Fabien Bruns, Dieter Fraboulet, Sandrine Hemming, Fiona J. Kirchhoff, Frank Sadoul, Rémy |
Sprache: | Englisch |
Titel: | PLoS Biology |
Bandnummer: | 20 |
Heft: | 6 |
Verlag/Plattform: | PLOS |
Erscheinungsjahr: | 2022 |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | In chemical synapses undergoing high frequency stimulation, vesicle components can be retrieved from the plasma membrane via a clathrin-independent process called activitydependent 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 clathrinindependent 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. |
DOI der Erstveröffentlichung: | 10.1371/journal.pbio.3001659 |
URL der Erstveröffentlichung: | https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001659 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-370791 hdl:20.500.11880/33658 http://dx.doi.org/10.22028/D291-37079 |
ISSN: | 1545-7885 |
Datum des Eintrags: | 25-Aug-2022 |
Bezeichnung des in Beziehung stehenden Objekts: | Supporting information |
In Beziehung stehendes Objekt: | https://journals.plos.org/plosbiology/article/file?type=supplementary&id=10.1371/journal.pbio.3001659.s001 https://journals.plos.org/plosbiology/article/file?type=supplementary&id=10.1371/journal.pbio.3001659.s002 https://journals.plos.org/plosbiology/article/file?type=supplementary&id=10.1371/journal.pbio.3001659.s003 https://journals.plos.org/plosbiology/article/file?type=supplementary&id=10.1371/journal.pbio.3001659.s004 https://journals.plos.org/plosbiology/article/file?type=supplementary&id=10.1371/journal.pbio.3001659.s005 https://journals.plos.org/plosbiology/article/file?type=supplementary&id=10.1371/journal.pbio.3001659.s006 https://journals.plos.org/plosbiology/article/file?type=supplementary&id=10.1371/journal.pbio.3001659.s007 https://journals.plos.org/plosbiology/article/file?type=supplementary&id=10.1371/journal.pbio.3001659.s008 https://journals.plos.org/plosbiology/article/file?type=supplementary&id=10.1371/journal.pbio.3001659.s009 https://journals.plos.org/plosbiology/article/file?type=supplementary&id=10.1371/journal.pbio.3001659.s010 https://journals.plos.org/plosbiology/article/file?type=supplementary&id=10.1371/journal.pbio.3001659.s011 https://journals.plos.org/plosbiology/article/file?type=supplementary&id=10.1371/journal.pbio.3001659.s012 |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Physiologie |
Professur: | M - Prof. Dr. Frank Kirchhoff |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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journal.pbio.3001659.pdf | 2,94 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons