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| Item Type: | Article |
|---|---|
| Title: | Selective endocytosis of Ca(2+)-permeable AMPARs by the Alzheimer's disease risk factor CALM bidirectionally controls synaptic plasticity |
| Creators: |
Azarnia Tehran, D.  ORCID: https://orcid.org/0000-0001-8955-7240, Kochlamazashvili, G., Pampaloni, N. P. ORCID: https://orcid.org/0000-0002-4066-0295, Sposini, S. ORCID: https://orcid.org/0000-0001-7681-8376, Shergill, J.K. ORCID: https://orcid.org/0000-0001-5506-2995, Lehmann, M. ORCID: https://orcid.org/0000-0002-8370-6353, Pashkova, N. ORCID: https://orcid.org/0000-0002-2191-4683, Schmidt, C., Löwe, D., Napieczynska, H., Heuser, A. ORCID: https://orcid.org/0000-0002-3334-960X, Plested, A.J.R. ORCID: https://orcid.org/0000-0001-6062-0832, Perrais, D. ORCID: https://orcid.org/0000-0002-5878-5408, Piper, R.C. ORCID: https://orcid.org/0000-0001-9995-5699, Haucke, V. ORCID: https://orcid.org/0000-0003-3119-6993 and Maritzen, T. ORCID: https://orcid.org/0000-0001-9995-5699
|
| 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(2+)-permeable (CP) versus heteromeric Ca(2+)-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. |
| Keywords: | AMPA Receptors, Alzheimer Disease, Endocytosis, Neuronal Plasticity, Risk Factors, Animals, Mammals |
| Source: | Science Advances |
| ISSN: | 2375-2548 |
| Publisher: | American Association for the Advancement of Science |
| Volume: | 8 |
| Number: | 21 |
| Page Range: | eabl5032 |
| Date: | 27 May 2022 |
| Official Publication: | https://doi.org/10.1126/sciadv.abl5032 |
| PubMed: | View item in PubMed |
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