Evidence map›Paper›PMID 25311365›Full record

ArticleMolecular psychiatry2015

Increased CYFIP1 dosage alters cellular and dendritic morphology and dysregulates mTOR.

A Oguro-Ando, C Rosensweig, E Herman, Y Nishimura, D Werling, B R Bill, J M Berg, F Gao, G Coppola, B S Abrahams and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 2 pooled it
6.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 121 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Brain, behavior, & immunity - health · 2026
    Article
  4. Article
  5. Review
  6. Control of microglial dynamics by the Arp2/3 complex and the autism- and schizophrenia-associated protein CYFIP1.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  7. ARP2/3 complex mediates the neuropathology of PTEN-deficient human neural cells downstream of mTORC1 and mTORC2 hyperactivation.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Genomics of severe and treatment-resistant obsessive-compulsive disorder treated with deep brain stimulation: A preliminary investigation.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2024
    Article
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  18. Review
  19. Article
  20. Overexpression of the autism candidate geneFrontiers in cellular neuroscience · 2023
    Article

13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 3 countries.

A Oguro-AndoNeurogenetics Program, Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
C RosensweigNeurogenetics Program, Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
E HermanNeurogenetics Program, Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Y NishimuraNeurogenetics Program, Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
D WerlingNeurogenetics Program, Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
B R BillNeurogenetics Program, Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
J M BergNeurogenetics Program, Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
F GaoNeurogenetics Program, Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
G CoppolaNeurogenetics Program, Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
B S AbrahamsNeurogenetics Program, Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
D H GeschwindNeurogenetics Program, Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
University of California, Los Angeles · USMie University · JPUniversity Medical Center Utrecht · NLYale University · US

Funding

A Comprehensive Approach to Identification of Autism Susceptibility GenesR01MH081754 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H · 2008 to 2012
$14.6M
Translational Neuroimaging CoreP30HD071593 · NICHD · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI WALKLEY, STEVEN UPSHAW · 2011 to 2015
$5.6M
Identification and Characterization of Asymmetrically-Expressed GenesR37MH060233 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H · 2006 to 2014
$5.3M
ASYMMETRICALLY EXPRESSED GENES IN THE DEVELOPING CEREBRUR01MH060233 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H · 1999 to 2003
$1.2M
NICHD NIH HHS P30 HD071593NICHD NIH HHS P30HD071593NIMH NIH HHS R01 MH060233NIMH NIH HHS R01 MH081754NIMH NIH HHS R01 MH081754-02RNIMH NIH HHS R37 MH060233NIMH NIH HHS R37 MH60233-06A1
6 · The paper itself

Abstract

Rare maternally inherited duplications at 15q11-13 are observed in ~1% of individuals with an autism spectrum disorder (ASD), making it among the most common causes of ASD. 15q11-13 comprises a complex region, and as this copy number variation encompasses many genes, it is important to explore individual genotype-phenotype relationships. Cytoplasmic FMR1-interacting protein 1 (CYFIP1) is of particular interest because of its interaction with Fragile X mental retardation protein (FMRP), its upregulation in transformed lymphoblastoid cell lines from patients with duplications at 15q11-13 and ASD and the presence of smaller overlapping deletions of CYFIP1 in patients with schizophrenia and intellectual disability. Here, we confirm that CYFIP1 is upregulated in transformed lymphoblastoid cell lines and demonstrate its upregulation in the post-mortem brain from 15q11-13 duplication patients for the first time. To investigate how increased CYFIP1 dosage might predispose to neurodevelopmental disease, we studied the consequence of its overexpression in multiple systems. We show that overexpression of CYFIP1 results in morphological abnormalities including cellular hypertrophy in SY5Y cells and differentiated mouse neuronal progenitors. We validate these results in vivo by generating a BAC transgenic mouse, which overexpresses Cyfip1 under the endogenous promotor, observing an increase in the proportion of mature dendritic spines and dendritic spine density. Gene expression profiling on embryonic day 15 suggested the dysregulation of mammalian target of rapamycin (mTOR) signaling, which was confirmed at the protein level. Importantly, similar evidence of mTOR-related dysregulation was seen in brains from 15q11-13 duplication patients with ASD. Finally, treatment of differentiated mouse neuronal progenitors with an mTOR inhibitor (rapamycin) rescued the morphological abnormalities resulting from CYFIP1 overexpression. Together, these data show that CYFIP1 overexpression results in specific cellular phenotypes and implicate modulation by mTOR signaling, further emphasizing its role as a potential convergent pathway in some forms of ASD.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsAutism Spectrum DisorderCells, CulturedChromosomes, Human, Pair 15Dendritic CellsDendritic SpinesDNA Copy Number VariationsFemaleFragile X Messenger Ribonucleoprotein 1Gene Expression RegulationHumansMiceMice, Inbred C57BLMice, TransgenicSignal TransductionAdaptor Proteins, Signal TransducingCYFIP1 protein, humanFragile X Messenger Ribonucleoprotein 1MTOR protein, humanTOR Serine-Threonine Kinases

Identifiers

PMID25311365
PMCPMC4409498
OpenAlexW2044692611

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.