Cited by 216Neuroscience and Neuropharmacology ResearchAdvanced Proteomics Techniques and ApplicationsGenetics and Neurodevelopmental Disorders

Metabolic Turnover of Synaptic Proteins: Kinetics, Interdependencies and Implications for Synaptic Maintenance

Open access
Cohen, Laurie D., Zuchman, Rina, Sorokina, Oksana, Müller, Anke, Dieterich, Daniela C., Armstrong, J. Douglas, Ziv, Tamar, Ziv, Noam E.·2013·PLoS ONE

Abstract

Chemical synapses contain multitudes of proteins, which in common with all proteins, have finite lifetimes and therefore need to be continuously replaced. Given the huge numbers of synaptic connections typical neurons form, the demand to maintain the protein contents of these connections might be expected to place considerable metabolic demands on each neuron. Moreover, synaptic proteostasis might differ according to distance from global protein synthesis sites, the availability of distributed protein synthesis facilities, trafficking rates and synaptic protein dynamics. To date, the turnover kinetics of synaptic proteins have not been studied or analyzed systematically, and thus metabolic demands or the aforementioned relationships remain largely unknown. In the current study we used dynamic Stable Isotope Labeling with Amino acids in Cell culture (SILAC), mass spectrometry (MS), Fluorescent Non-Canonical Amino acid Tagging (FUNCAT), quantitative immunohistochemistry and bioinformatics to systematically measure the metabolic half-lives of hundreds of synaptic proteins, examine how these depend on their pre/postsynaptic affiliation or their association with particular molecular complexes, and assess the metabolic load of synaptic proteostasis. We found that nearly all synaptic proteins identified here exhibited half-lifetimes in the range of 2-5 days. Unexpectedly, metabolic turnover rates were not significantly different for presynaptic and postsynaptic proteins, or for proteins for which mRNAs are consistently found in dendrites. Some functionally or structurally related proteins exhibited very similar turnover rates, indicating that their biogenesis and degradation might be coupled, a possibility further supported by bioinformatics-based analyses. The relatively low turnover rates measured here (∼0.7% of synaptic protein content per hour) are in good agreement with imaging-based studies of synaptic protein trafficking, yet indicate that the metabolic load synaptic protein turnover places on individual neurons is very substantial.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0063191

Cites

86 of 86 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • CaMKII is known to turn over rapidly, with a half-life of 2-4 days.

    “In particular, CaMKII is known to turn over rapidly, with a half-life of 2–4 days (403–405).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [403]

    The Results table reports a 3.81-day half-life for CaMKIIβ2 in cultured cortical neurons, within the claimed range. It also reports 5.03 days for CaMKIIγ, so the 2–4-day range is not supported for CaMKII generally. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • Most synaptic proteins generally have half-lives of 2-5 days.

    “Although memories can last for the entire span of an animal’s life, most synaptic proteins generally have half-lives of 2–5 days (403, 404).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [403]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Cohen, L. D., Zuchman, R., Sorokina, O., Müller, A., Dieterich, D. C., Armstrong, J. D., Ziv, T., & Ziv, N. E.
Affiliations
  • Technion – Israel Institute of Technology (IL)
  • University of Edinburgh (GB)
  • Otto-von-Guericke-Universität Magdeburg (DE)
Corresponding author
Ziv, Noam E.
Venue
PLoS ONE
Published
2013-05-02
Volume
8
Issue
5
Pages
e63191
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2050606229
Cited by
215
References
86
Citations by year
2026: 8 · 2025: 10 · 2024: 16 · 2023: 16 · 2022: 16 · 2021: 18 · 2020: 21 · 2019: 26 · 2018: 20 · 2017: 20 · 2016: 11 · 2015: 15 · 2014: 15 · 2013: 2 · 2012: 1
FWCI
7.03
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
Funders
  • European Commission (241498)
  • University of Haifa
  • Technion-Israel Institute of Technology
  • Universität Ulm
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
synaptic proteins, protein turnover, protein half-life, presynaptic proteins, postsynaptic proteins, dendritic mRNA, protein degradation, protein synthesis, synapse maintenance, protein complex association
MeSH terms
Animals, Cell Compartmentation, Kinetics, Neurons, Proteins, Synapses, Rats, Wistar, Protein Transport, Proteomics, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review