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

Autor: Kallergi E; Department of Fundamental Neurosciences, University of Lausanne, Lausanne, 1005, Switzerland., Daskalaki AD; Department of Fundamental Neurosciences, University of Lausanne, Lausanne, 1005, Switzerland., Kolaxi A; Department of Fundamental Neurosciences, University of Lausanne, Lausanne, 1005, Switzerland., Camus C; University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, F-33000, Bordeaux, France., Ioannou E; School of Biological Sciences, University of Crete, Heraklion, 70013, Greece., Mercaldo V; Department of Fundamental Neurosciences, University of Lausanne, Lausanne, 1005, Switzerland., Haberkant P; Proteomic Core Facility (PCF), European Molecular Biology Laboratory (EMBL), Heidelberg, Germany., Stein F; Proteomic Core Facility (PCF), European Molecular Biology Laboratory (EMBL), Heidelberg, Germany., Sidiropoulou K; School of Biological Sciences, University of Crete, Heraklion, 70013, Greece., Dalezios Y; School of Medicine, University of Crete, Heraklion, 71003, Greece.; Institute of Applied and Computational Mathematics (IACM), Foundation for Research and Technology-Hellas (FORTH), Heraklion, Greece., Savitski MM; Proteomic Core Facility (PCF), European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.; Genome Biology Unit, European Molecular Biology Laboratory (EMBL), University of Rome Tor Vergata, Rome, 00133, Italy., Bagni C; Department of Fundamental Neurosciences, University of Lausanne, Lausanne, 1005, Switzerland.; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, 00133, Italy., Choquet D; University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, F-33000, Bordeaux, France.; University of Bordeaux, CNRS, INSERM, Bordeaux Imaging Center, BIC, UMS 3420, US 4, F-33000, Bordeaux, France., Hosy E; University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, F-33000, Bordeaux, France., Nikoletopoulou V; Department of Fundamental Neurosciences, University of Lausanne, Lausanne, 1005, Switzerland. vassiliki.nikoletopoulou@unil.ch.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Feb 03; Vol. 13 (1), pp. 680. Date of Electronic Publication: 2022 Feb 03.
DOI: 10.1038/s41467-022-28301-z
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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