A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P
Open accessAbstract
The absence of the fragile X mental retardation protein (FMRP), encoded by the FMR1 gene, is responsible for pathologic manifestations in the Fragile X Syndrome, the most frequent cause of inherited mental retardation. FMRP is an RNA-binding protein associated with polysomes as part of a messenger ribonucleoprotein (mRNP) complex. Although its function is poorly understood, various observations suggest a role in local protein translation at neuronal dendrites and in dendritic spine maturation. We present here the identification of CYFIP1/2 ( Cy toplasmic F MRP I nteracting P roteins) as FMRP interactors. CYFIP1/2 share 88% amino acid sequence identity and represent the two members in humans of a highly conserved protein family. Remarkably, whereas CYFIP2 also interacts with the FMRP-related proteins FXR1P/2P, CYFIP1 interacts exclusively with FMRP. FMRP–CYFIP interaction involves the domain of FMRP also mediating homo- and heteromerization, thus suggesting a competition between interaction among the FXR proteins and interaction with CYFIP. CYFIP1/2 are proteins of unknown function, but CYFIP1 has recently been shown to interact with the small GTPase Rac1, which is implicated in development and maintenance of neuronal structures. Consistent with FMRP and Rac1 localization in dendritic fine structures, CYFIP1/2 are present in synaptosomal extracts.
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CYFIP1 interacts with FMRP and with the translation initiation factor eIF4E.
“CYFIP1 interacts with the Fragile X mental retardation protein (FMRP, encoded by the FMR1 gene), whose absence causes Fragile X syndrome, and with the translation initiation factor eIF4E.”
From New insights into the regulatory function of CYFIP1 in the context of WAVE- and FMRP-containing complexes (2017) · cites this paper as Schenck et al., 2001
The Interaction Between FMRP and CYFIP1 section (page not provided) reports experimental evidence that CYFIP1 interacts with FMRP. The cited paper does not report an interaction between CYFIP1 and eIF4E; its Discussion addresses translational regulation only as a proposed role. (LLM, conf=0.89)
Experimental — accuracy not yet measuredCYFIP1 is a key functional partner of FMRP.
“A key functional partner of FMRP is the cytoplasmic FMRP-interacting protein 1, CYFIP1 (Napoli et al., 2008, Schenck et al., 2003, Schenck et al., 2001) also known as “specific Rac1-activated” (SRA1) protein (Kobayashi et al., 1998).”
From CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation (2013) · cites this paper as Schenck et al., 2001
The paper establishes that CYFIP1 interacts selectively with FMRP (Abstract; Discussion). But it describes CYFIP1’s function as unknown and proposes, rather than demonstrates, a role in regulating FMRP, so “key functional partner” overstates what this source establishes. Page numbers are not available in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe CYFIP1-FMRP interaction was initially identified by two-hybrid screening in yeast.
“The CYFIP1-FMRP interaction, initially identified by two-hybrid screening in yeast (Bardoni et al., 1999; Schenck et al., 2001), was confirmed by GST pull-down and immunoprecipitation both in mouse and fly cell lines and tissues (Schenck et al., 2001, 2003; De Rubeis et al., 2013).”
From New insights into the regulatory function of CYFIP1 in the context of WAVE- and FMRP-containing complexes (2017) · cites this paper as Schenck et al., 2001
While both CYFIP1 and CYFIP2 interact with FMRP, only CYFIP2 interacts with FXR1P and FXR2P.
“(i) while both CYFIP1 and CYFIP2 interact with FMRP, only CYFIP2 interacts with FXR1P and FXR2P, the two paralogs and interactors of FMRP (Schenck et al., 2001);”
From New insights into the regulatory function of CYFIP1 in the context of WAVE- and FMRP-containing complexes (2017) · cites this paper as Schenck et al., 2001
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“CYFIP1 and CYFIP2 are members of a family of proteins interacting with the Fragile X mental retardation protein (FMRP, encoded by FMR1 ) in mammals, as well as in the fly (Abekhoukh and Bardoni, 2014; Schenck et al., 2001, 2003).”
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- Authors
- Schenck, A., Bardoni, B., Moro, A., Bagni, C., & Mandel, J.-L.
- Affiliations
- University of Rome Tor Vergata (IT)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-07-03
- Volume
- 98
- Issue
- 15
- Pages
- 8844-8849
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC37523
- OpenAlex
- W2048108096
- Cited by
- 356
- References
- 5
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 18 · 2023: 11 · 2022: 14 · 2021: 18 · 2020: 19 · 2019: 13 · 2018: 16 · 2017: 16 · 2016: 13 · 2015: 16 · 2014: 20 · 2013: 15 · 2012: 8
- FWCI
- 10.04
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- HAL (submittedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Funders
- FRAXA Research Foundation
- Centre National de la Recherche Scientifique
- 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 › RNA Research and Splicing
- Keywords
- FMRP, CYFIP1, CYFIP2, FXR1P, protein-protein interaction, fragile X syndrome, RNA-binding proteins, messenger ribonucleoprotein, polysomes, dendritic translation, dendritic spine maturation, Rac1, synapses, protein families
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Cell Extracts, Cell Fractionation, Cell Line, Chlorocebus aethiops, Exons, HeLa Cells, Humans, Molecular Sequence Data, Nerve Tissue Proteins, Proteins, Rabbits, Recombinant Fusion Proteins, RNA, Gene Expression, RNA-Binding Proteins, Conserved Sequence, DNA, Complementary, Spodoptera, COS Cells, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1
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