IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28301-z.html
   My bibliography  Save this article

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

Author

Listed:
  • Emmanouela Kallergi

    (University of Lausanne)

  • Akrivi-Dimitra Daskalaki

    (University of Lausanne)

  • Angeliki Kolaxi

    (University of Lausanne)

  • Come Camus

    (University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience)

  • Evangelia Ioannou

    (University of Crete)

  • Valentina Mercaldo

    (University of Lausanne)

  • Per Haberkant

    (European Molecular Biology Laboratory (EMBL))

  • Frank Stein

    (European Molecular Biology Laboratory (EMBL))

  • Kyriaki Sidiropoulou

    (University of Crete)

  • Yannis Dalezios

    (University of Crete
    Foundation for Research and Technology—Hellas (FORTH))

  • Mikhail M. Savitski

    (European Molecular Biology Laboratory (EMBL)
    University of Rome Tor Vergata)

  • Claudia Bagni

    (University of Lausanne
    University of Rome Tor Vergata)

  • Daniel Choquet

    (University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience
    University of Bordeaux, CNRS, INSERM, Bordeaux Imaging Center)

  • Eric Hosy

    (University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience)

  • Vassiliki Nikoletopoulou

    (University of Lausanne)

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.

Suggested Citation

  • Emmanouela Kallergi & Akrivi-Dimitra Daskalaki & Angeliki Kolaxi & Come Camus & Evangelia Ioannou & Valentina Mercaldo & Per Haberkant & Frank Stein & Kyriaki Sidiropoulou & Yannis Dalezios & Mikhail , 2022. "Dendritic autophagy degrades postsynaptic proteins and is required for long-term synaptic depression in mice," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28301-z
    DOI: 10.1038/s41467-022-28301-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28301-z
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-28301-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Patrick Lüningschrör & Beyenech Binotti & Benjamin Dombert & Peter Heimann & Angel Perez-Lara & Carsten Slotta & Nadine Thau-Habermann & Cora R. von Collenberg & Franziska Karl & Markus Damme & Arie H, 2017. "Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    2. Hongmei Shen & Huiwen Zhu & Debabrata Panja & Qinhua Gu & Zheng Li, 2020. "Autophagy controls the induction and developmental decline of NMDAR-LTD through endocytic recycling," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
    3. Joseph D. Mancias & Xiaoxu Wang & Steven P. Gygi & J. Wade Harper & Alec C. Kimmelman, 2014. "Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy," Nature, Nature, vol. 509(7498), pages 105-109, May.
    4. Benjamin Compans & Come Camus & Emmanouela Kallergi & Silvia Sposini & Magalie Martineau & Corey Butler & Adel Kechkar & Remco V. Klaassen & Natacha Retailleau & Terrence J. Sejnowski & August B. Smit, 2021. "NMDAR-dependent long-term depression is associated with increased short term plasticity through autophagy mediated loss of PSD-95," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Dan Fu & Wenming Wang & Yan Zhang & Fan Zhang & Pinyi Yang & Chun Yang & Yufei Tian & Renqi Yao & Jingwu Jian & Zixian Sun & Nan Zhang & Zhiyu Ni & Zihe Rao & Lei Zhao & Yu Guo, 2024. "Self-assembling nanoparticle engineered from the ferritinophagy complex as a rabies virus vaccine candidate," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Di-Yang Sun & Wen-Bin Wu & Jian-Jin Wu & Yu Shi & Jia-Jun Xu & Shen-Xi Ouyang & Chen Chi & Yi Shi & Qing-Xin Ji & Jin-Hao Miao & Jiang-Tao Fu & Jie Tong & Ping-Ping Zhang & Jia-Bao Zhang & Zhi-Yong Li, 2024. "Pro-ferroptotic signaling promotes arterial aging via vascular smooth muscle cell senescence," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    3. Xiaoting Zhou & You-Kyung Lee & Xianting Li & Henry Kim & Carlos Sanchez-Priego & Xian Han & Haiyan Tan & Suiping Zhou & Yingxue Fu & Kerry Purtell & Qian Wang & Gay R. Holstein & Beisha Tang & Junmin, 2024. "Integrated proteomics reveals autophagy landscape and an autophagy receptor controlling PKA-RI complex homeostasis in neurons," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Wei Yang & Bo Mu & Jing You & Chenyu Tian & Huachao Bin & Zhiqiang Xu & Liting Zhang & Ronggang Ma & Ming Wu & Guo Zhang & Chong Huang & Linli Li & Zhenhua Shao & Lunzhi Dai & Laurent Désaubry & Sheng, 2022. "Non-classical ferroptosis inhibition by a small molecule targeting PHB2," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Amy-Jayne Hutchings & Bita Hambrecht & Alexander Veh & Neha Jadhav Giridhar & Abdolhossein Zare & Christina Angerer & Thorben Ohnesorge & Maren Schenke & Bhuvaneish T. Selvaraj & Siddharthan Chandran , 2024. "Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagy," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    6. Xinyi Shan & Jiahuan Li & Jiahao Liu & Baoli Feng & Ting Zhang & Qian Liu & Huixin Ma & Honghong Wu & Hao Wu, 2023. "Targeting ferroptosis by poly(acrylic) acid coated Mn3O4 nanoparticles alleviates acute liver injury," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. Fabian Hoelzgen & Thuy T. P. Nguyen & Elina Klukin & Mohamed Boumaiza & Ayush K. Srivastava & Elizabeth Y. Kim & Ran Zalk & Anat Shahar & Sagit Cohen-Schwartz & Esther G. Meyron-Holtz & Fadi Bou-Abdal, 2024. "Structural basis for the intracellular regulation of ferritin degradation," Nature Communications, Nature, vol. 15(1), pages 1-10, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28301-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.