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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 Name: | Azarnia Tehran, D. and Kochlamazashvili, G. and Pampaloni, N. P. and Sposini, S. and Shergill, J.K. and Lehmann, M. and Pashkova, N. and Schmidt, C. and Löwe, D. and Napieczynska, H. and Heuser, A. and Plested, A.J.R. and Perrais, D. and Piper, R.C. and Haucke, V. and Maritzen, T. |
| 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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