Journal article
Selective endocytosis of Ca 2+ -permeable AMPARs by the Alzheimer's disease risk factor CALM bidirectionally controls synaptic plasticity
Science advances, Vol.8(21), p.eabl5032
05/27/2022
DOI: 10.1126/sciadv.abl5032
PMCID: PMC9132451
PMID: 35613266
Abstract
AMPA-type glutamate receptors (AMPARs) mediate fast excitatory neurotransmission, and the plastic modulation of their surface levels determines synaptic strength. AMPARs of different subunit compositions fulfill distinct roles in synaptic long-term potentiation (LTP) and depression (LTD) to enable learning. Largely unknown endocytic mechanisms mediate the subunit-selective regulation of the surface levels of GluA1-homomeric Ca
-permeable (CP) versus heteromeric Ca
-impermeable (CI) AMPARs. Here, we report that the Alzheimer's disease risk factor CALM controls the surface levels of CP-AMPARs and thereby reciprocally regulates LTP and LTD in vivo to modulate learning. We show that CALM selectively facilitates the endocytosis of ubiquitinated CP-AMPARs via a mechanism that depends on ubiquitin recognition by its ANTH domain but is independent of clathrin. Our data identify CALM and related ANTH domain-containing proteins as the core endocytic machinery that determines the surface levels of CP-AMPARs to bidirectionally control synaptic plasticity and modulate learning in the mammalian brain.
Details
- Title: Subtitle
- Selective endocytosis of Ca 2+ -permeable AMPARs by the Alzheimer's disease risk factor CALM bidirectionally controls synaptic plasticity
- Creators
- Domenico Azarnia Tehran - Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Roessle-Straße 10, 13125 Berlin, GermanyGaga Kochlamazashvili - Leibniz-Forschungsinstitut für Molekulare PharmakologieNiccolò P Pampaloni - Leibniz-Forschungsinstitut für Molekulare PharmakologieSilvia Sposini - Interdisciplinary Institute for NeuroScienceJasmeet Kaur Shergill - Leibniz-Forschungsinstitut für Molekulare PharmakologieMartin Lehmann - Leibniz-Forschungsinstitut für Molekulare PharmakologieNatalya Pashkova - Roy J. and Lucille A. Carver College of MedicineClaudia Schmidt - Leibniz-Forschungsinstitut für Molekulare PharmakologieDelia Löwe - Leibniz-Forschungsinstitut für Molekulare PharmakologieHanna Napieczynska - Max Delbrück Center for Molecular MedicineArnd Heuser - Max Delbrück Center for Molecular MedicineAndrew J R Plested - Leibniz-Forschungsinstitut für Molekulare PharmakologieDavid Perrais - Interdisciplinary Institute for NeuroScienceRobert C Piper - Roy J. and Lucille A. Carver College of MedicineVolker Haucke - Leibniz-Forschungsinstitut für Molekulare PharmakologieTanja Maritzen - Leibniz-Forschungsinstitut für Molekulare Pharmakologie
- Resource Type
- Journal article
- Publication Details
- Science advances, Vol.8(21), p.eabl5032
- DOI
- 10.1126/sciadv.abl5032
- PMID
- 35613266
- PMCID
- PMC9132451
- ISSN
- 2375-2548
- eISSN
- 2375-2548
- Language
- English
- Date published
- 05/27/2022
- Academic Unit
- Molecular Physiology and Biophysics; Medicine Administration; Internal Medicine
- Record Identifier
- 9984297510702771
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