Altered presynaptic function and number of mitochondria in the medial prefrontal cortex of adult Cyfip2 heterozygous mice
Open accessAbstract
Variants of the cytoplasmic FMR1-interacting protein (CYFIP) gene family, CYFIP1 and CYFIP2, are associated with numerous neurodevelopmental and neuropsychiatric disorders. According to several studies, CYFIP1 regulates the development and function of both pre- and post-synapses in neurons. Furthermore, various studies have evaluated CYFIP2 functions in the postsynaptic compartment, such as regulating dendritic spine morphology; however, no study has evaluated whether and how CYFIP2 affects presynaptic functions. To address this issue, in this study, we have focused on the presynapses of layer 5 neurons of the medial prefrontal cortex (mPFC) in adult Cyfip2 heterozygous (Cyfip2+/−) mice. Electrophysiological analyses revealed an enhancement in the presynaptic short-term plasticity induced by high-frequency stimuli in Cyfip2+/− neurons compared with wild-type neurons. Since presynaptic mitochondria play an important role in buffering presynaptic Ca 2+, which is directly associated with the short-term plasticity, we analyzed presynaptic mitochondria using electron microscopic images of the mPFC. Compared with wild-type mice, the number, but not the volume or cristae density, of mitochondria in both presynaptic boutons and axonal processes in the mPFC layer 5 of Cyfip2+/− mice was reduced. Consistent with an identification of mitochondrial proteins in a previously established CYFIP2 interactome, CYFIP2 was detected in a biochemically enriched mitochondrial fraction of the mouse mPFC. Collectively, these results suggest roles for CYFIP2 in regulating presynaptic functions, which may involve presynaptic mitochondrial changes.
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.
Integrity signals
Registry
Cites
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.
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?
CYFIP2 regulates presynaptic functions presumably via the regulation of presynaptic mitochondria number in the adult brain.
“CYFIP2 regulates presynaptic functions presumably via the regulation of presynaptic mitochondria number in the adult brain74.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [74]
The Main text reports altered presynaptic short-term plasticity and fewer presynaptic mitochondria in layer 5 of the medial prefrontal cortex of adult Cyfip2 heterozygous mice. It speculates that the reduced mitochondrial number may contribute to the functional change, consistent with the claim’s hedge, but does not establish this mechanism across the adult brain. (LLM, conf=0.83)
Experimental — accuracy not yet measured
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
Short-Term Presynaptic Plasticity
Regehr, W. G. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005702 · Cited by 482 · see citing works
De Rubeis, S., Pasciuto, E., Li, K. W., Fernández, E., Di Marino, D., Buzzi, A., Ostroff, L. E., Klann, E., Zwartkruis, F. J. T., Komiyama, N. H., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.06.039 · Cited by 296 · see citing works
Davenport, E. C., Szulc, B. R., Drew, J., Taylor, J., Morgan, T., Higgs, N. F., López-Doménech, G., & Kittler, J. T. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.01.092 · Cited by 125 · see citing works
CYFIP family proteins between autism and intellectual disability: links with Fragile X syndrome
Abekhoukh, S., & Bardoni, B. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00081 · Cited by 110 · see citing works
Flagged first, then by citations
Research works printed but not linked: 15
- [1]Zhang Y Lee Y Han K Neuronal function and dysfunction of CYFIP2: from actin dynamics to early infantile epileptic encephalopathy BMB Rep 2019 52 5 304 311 10.5483/BMBRep.2019.52.5.097 30982501 PMC6549915 · DOI
- [3]Nakashima M Kato M Aoto K Shiina M Belal H Mukaida S De novo hotspot variants in CYFIP2 cause early-onset epileptic encephalopathy Ann Neurol 2018 83 4 794 806 10.1002/ana.25208 29534297 · DOI · Paper page
- [4]Hsiao K Harony-Nicolas H Buxbaum JD Bozdagi-Gunal O Benson DL Cyfip1 regulates presynaptic activity during development J Neurosci 2016 36 5 1564 1576 10.1523/JNEUROSCI.0511-15.2016 26843638 PMC4737770 · DOI · Paper page
- [7]Han K Chen H Gennarino VA Richman R Lu HC Zoghbi HY Fragile X-like behaviors and abnormal cortical dendritic spines in cytoplasmic FMR1-interacting protein 2-mutant mice Hum Mol Genet 2015 24 7 1813 1823 10.1093/hmg/ddu595 25432536 PMC4355018 · DOI · Paper page
- [8]Lee SH, Zhang Y, Park J, Kim B, Kim Y, Lee SH, et al. Haploinsufficiency of Cyfip2 causes lithium-responsive prefrontal dysfunction. Ann Neurol. 2020. 10.1002/ana.25827. 32562430 · DOI
- [9]Lee Y Kim D Ryu JR Zhang Y Kim S Kim Y Phosphorylation of CYFIP2, a component of the WAVE-regulatory complex, regulates dendritic spine density and neurite outgrowth in cultured hippocampal neurons potentially by affecting the complex assembly Neuroreport. 2017 28 12 749 754 10.1097/WNR.0000000000000838 28692454 · DOI
- [11]Devine MJ Kittler JT Mitochondria at the neuronal presynapse in health and disease Nat Rev Neurosci 2018 19 2 63 80 10.1038/nrn.2017.170 29348666 · DOI
- [12]Kwon SK Sando R 3rd Lewis TL Hirabayashi Y Maximov A Polleux F LKB1 regulates mitochondria-dependent presynaptic calcium clearance and neurotransmitter release properties at excitatory synapses along cortical axons PLoS Biol 2016 14 7 e1002516 10.1371/journal.pbio.1002516 27429220 PMC4948842 · DOI
- [13]Kanellopoulos AK Mariano V Spinazzi M Woo YJ McLean C Pech U Aralar sequesters GABA into hyperactive mitochondria Causing Social Behavior Deficits Cell 2020 180 6 1178 1197 10.1016/j.cell.2020.02.044 32200800 · DOI
- [14]Leveille CF Mikhaeil JS Turner KD Silvera S Wilkinson J Fajardo VA Mitochondrial cristae density: a dynamic entity that is critical for energy production and metabolic power in skeletal muscle J Physiol 2017 595 9 2779 2780 10.1113/JP274158 28217967 PMC5407988 · DOI
- [15]Lee Y Zhang Y Kang H Bang G Kim Y Kang HR Epilepsy-and intellectual disability-associated CYFIP2 interacts with both actin regulators and RNA-binding proteins in the neonatal mouse forebrain Biochem Biophys Res Commun 2020 529 1 1 6 10.1016/j.bbrc.2020.05.221 32560809 · DOI
- [16]Sheng ZH Cai Q Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration Nat Rev Neurosci 2012 13 2 77 93 10.1038/nrn3156 22218207 PMC4962561 · DOI
- [17]Calvo SE Clauser KR Mootha VK MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins Nucleic Acids Res 2016 44 D1 D1251 D1257 10.1093/nar/gkv1003 26450961 PMC4702768 · DOI · Paper page
- [18]Cotter D Guda P Fahy E Subramaniam S MitoProteome: mitochondrial protein sequence database and annotation system Nucleic Acids Res 2004 32 D463 D4D7 10.1093/nar/gkh048 14681458 PMC308782 · DOI
- [19]Savojardo C Bruciaferri N Tartari G Martelli PL Casadio R DeepMito: accurate prediction of protein sub-mitochondrial localization using convolutional neural networks Bioinformatics. 2020 36 1 56 64 10.1093/bioinformatics/btz512 31218353 PMC6956790 · DOI
Cited by
Sorted by citations
The WAVE complex in developmental and adulthood brain disorders
Kim, H.-G., Berdasco, C., Nairn, A. C., & Kim, Y. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01386-w · Cited by 8 · see citing works
Self-citation
- Authors
- Kim, G. H., Zhang, Y., Kang, H. R., Lee, S.-H., Shin, J., Lee, C. H., Kang, H., Ma, R., Jin, C., Kim, Y., Kim, S. Y., Kwon, S.-K., Choi, S.-Y., Lee, K. J., & Han, K.
- Affiliations
- Korea Brain Research Institute (KR)
- Korea University (KR)
- Seoul National University (KR)
- Korea Institute of Science and Technology (KR)
- Daegu Gyeongbuk Institute of Science and Technology (KR)
- Corresponding author
- Choi, Se-Young
- Lee, Kea Joo
- Han, Kihoon
- ORCID
- Venue
- Molecular Brain
- Published
- 2020-09-11
- Volume
- 13
- Issue
- 1
- Pages
- 123-123
- ISSN
- 1756-6606 (ISSN-L)
- PMC
- PMC7488858
- OpenAlex
- W3086977165
- Cited by
- 14
- References
- 4
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 2
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Molecular Brain (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- National Research Foundation of Korea (NRF-2018R1C1B6001235, NRF-2018M3C7A1024603, NRF-2017M3C7A1048086, NRF-2020R1A2C3011464)
- KBRI Basic Research Programs (20-BR-01-08, 20-BR-04-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- CYFIP2, presynaptic function, presynaptic mitochondria, medial prefrontal cortex, layer 5 neurons, short-term plasticity, heterozygous mice, neuropsychiatric disorders
- MeSH terms
- Animals, Heterozygote, Mitochondria, Prefrontal Cortex, Presynaptic Terminals, Adaptor Proteins, Signal Transducing, Mice
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
