Dendritic autophagy degrades postsynaptic proteins and is required for long-term synaptic depression in mice.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_CF76038E769E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dendritic autophagy degrades postsynaptic proteins and is required for long-term synaptic depression in mice.
Journal
Nature communications
Author(s)
Kallergi E., Daskalaki A.D., Kolaxi A., Camus C., Ioannou E., Mercaldo V., Haberkant P., Stein F., Sidiropoulou K., Dalezios Y., Savitski M.M., Bagni C., Choquet D., Hosy E., Nikoletopoulou V.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
03/02/2022
Peer-reviewed
Oui
Volume
13
Number
1
Pages
680
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
The pruning of dendritic spines during development requires autophagy. This process is facilitated by long-term depression (LTD)-like mechanisms, which has led to speculation that LTD, a fundamental form of synaptic plasticity, also requires autophagy. Here, we show that the induction of LTD via activation of NMDA receptors or metabotropic glutamate receptors initiates autophagy in the postsynaptic dendrites in mice. Dendritic autophagic vesicles (AVs) act in parallel with the endocytic machinery to remove AMPA receptor subunits from the membrane for degradation. During NMDAR-LTD, key postsynaptic proteins are sequestered for autophagic degradation, as revealed by quantitative proteomic profiling of purified AVs. Pharmacological inhibition of AV biogenesis, or conditional ablation of atg5 in pyramidal neurons abolishes LTD and triggers sustained potentiation in the hippocampus. These deficits in synaptic plasticity are recapitulated by knockdown of atg5 specifically in postsynaptic pyramidal neurons in the CA1 area. Conducive to the role of synaptic plasticity in behavioral flexibility, mice with autophagy deficiency in excitatory neurons exhibit altered response in reversal learning. Therefore, local assembly of the autophagic machinery in dendrites ensures the degradation of postsynaptic components and facilitates LTD expression.
Pubmed
Open Access
Yes
Create date
12/02/2022 16:03
Last modification date
23/11/2022 8:15
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