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Cited by 28Genetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology ResearchAutism Spectrum Disorder Research

FMRP and CYFIP1 at the Synapse and Their Role in Psychiatric Vulnerability

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Clifton, Nicholas E., Thomas, Kerrie L., Wilkinson, Lawrence S., Hall, Jeremy, Trent, Simon·2020·Complex Psychiatry
DOI 10.1159/000506858PMC PMC7673588
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Abstract

There is increasing awareness of the role genetic risk variants have in mediating vulnerability to psychiatric disorders such as schizophrenia and autism. Many of these risk variants encode synaptic proteins, influencing biological pathways of the postsynaptic density and, ultimately, synaptic plasticity. Fragile-X mental retardation 1 (FMR1) and cytoplasmic fragile-X mental retardation protein (FMRP)-interacting protein 1 (CYFIP1) contain 2 such examples of highly penetrant risk variants and encode synaptic proteins with shared functional significance. In this review, we discuss the biological actions of FMRP and CYFIP1, including their regulation of (i) protein synthesis and specifically FMRP targets, (ii) dendritic and spine morphology, and (iii) forms of synaptic plasticity such as long-term depression. We draw upon a range of preclinical studies that have used genetic dosage models of FMR1 and CYFIP1 to determine their biological function. In parallel, we discuss how clinical studies of fragile X syndrome or 15q11.2 deletion patients have informed our understanding of FMRP and CYFIP1, and highlight the latest psychiatric genomic findings that continue to implicate FMRP and CYFIP1. Lastly, we assess the current limitations in our understanding of FMRP and CYFIP1 biology and how they must be addressed before mechanism-led therapeutic strategies can be developed for psychiatric disorders.

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Authors
Clifton, N. E., Thomas, K. L., Wilkinson, L. S., Hall, J., & Trent, S.
Affiliations
  • Cardiff University (GB)
  • Keele University (GB)
Corresponding author
Trent, Simon
ORCID
Venue
Complex Psychiatry
Publisher
S. Karger AG
Published
2020
Volume
6
Issue
1-2
Pages
5-19
ISSN
  • 2673-298X (ISSN-L)
  • 2673-3005
DOI
10.1159/000506858
PMC
PMC7673588
OpenAlex
W3010485710
Cited by
28
References
225
Citations by year
2026: 4 · 2025: 7 · 2024: 4 · 2023: 8 · 2022: 3 · 2021: 1 · 2020: 1
FWCI
0.46
Type
journal article
Language
en
Open access
Licence
Locations
  • Complex Psychiatry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
Funders
  • Wellcome Trust (100202/Z/12/Z)
  • Medical Research Council (MR/L010305/1)
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 › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Keywords
FMRP, CYFIP1, fragile X syndrome, synaptic proteins, postsynaptic density, synaptic plasticity, long-term depression, protein synthesis regulation, dendritic spine morphology, genetic risk variants, schizophrenia, autism spectrum disorder, psychiatric vulnerability

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