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  Dynamic bi-directional phosphorylation events associated with the reciprocal regulation of synapses during homeostatic up- and down-scaling

Desch, K., Langer, J. D., & Schuman, E. M. (2021). Dynamic bi-directional phosphorylation events associated with the reciprocal regulation of synapses during homeostatic up- and down-scaling. Cell Rep., 36(8): 109583. doi:10.1016/j.celrep.2021.109583.

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1-s2.0-S2211124721010172-main.pdf (Publisher version), 5MB
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2021
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2021 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

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 Creators:
Desch, Kristina1, Author
Langer, Julian D.1, Author           
Schuman, Erin M.1, Author           
Affiliations:
1Synaptic Plasticity Department, Max Planck Institute for Brain Research, Max Planck Society, ou_2461710              

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Free keywords: PTM; homeostatic scaling; mass spectrometry; phosphoproteomics; post-translational modification; protein phosphorylation; proteomics; synaptic plasticity.
 Abstract: Homeostatic synaptic scaling allows for bi-directional adjustment of the strength of synaptic connections in response to changes in their input. Protein phosphorylation modulates many neuronal processes, but it has not been studied on a global scale during synaptic scaling. Here, we use liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses to measure changes in the phosphoproteome in response to up- or down-scaling in cultured cortical neurons over minutes to 24 h. Of ~45,000 phosphorylation events, ~3,300 (associated with 1,285 phosphoproteins) are regulated by homeostatic scaling. Activity-sensitive phosphoproteins are predominantly located at synapses and involved in cytoskeletal reorganization. We identify many early phosphorylation events that could serve as sensors for the activity offset as well as late and/or persistent phosphoregulation that could represent effector mechanisms driving the homeostatic response. Much of the persistent phosphorylation is reciprocally regulated by up- or down-scaling, suggesting that mechanisms underlying these two poles of synaptic regulation make use of a common signaling axis.

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Language(s): eng - English
 Dates: 2021-02-122021-07-292021-08-24
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.celrep.2021.109583
PMID: 34433048
 Degree: -

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Project name : ERC-AdG NeuroRibo
Grant ID : 743216
Funding program : Horizon 2020 (H2020)
Funding organization : European Commission (EC)
Project name : SFB 1080: Molecular and Cellular Mechanisms of Neural Homeostasis
Grant ID : 221828878
Funding program : Collaborative Research Centres
Funding organization : Deutsche Forschungsgemeinschaft (DFG)
Project name : SFB 902: Molecular Principles of RNA-based Regulation.
Grant ID : 161793742
Funding program : Collaborative Research Centres
Funding organization : Deutsche Forschungsgemeinschaft (DFG)

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Title: Cell Rep.
Source Genre: Journal
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Publ. Info: Maryland Heights, MO : Cell Press
Pages: - Volume / Issue: 36 (8) Sequence Number: 109583 Start / End Page: - Identifier: ISSN: 2211-1247
CoNE: https://pure.mpg.de/cone/journals/resource/2211-1247