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Cytoplasmic FMR1 interacting protein (CYFIP) family members and their function in neural development and disorders

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Abstract

In humans, the cytoplasmic FMR1 interacting protein (CYFIP) family is composed of CYFIP1 and CYFIP2. Despite their high similarity and shared interaction with many partners, CYFIP1 and CYFIP2 act at different points in cellular processes. CYFIP1 and CYFIP2 have different expression levels in human tissues, and knockout animals die at different time points of development. CYFIP1, similar to CYFIP2, acts in the WAVE regulatory complex (WRC) and plays a role in actin dynamics through the activation of the Arp2/3 complex and in a posttranscriptional regulatory complex with the fragile X mental retardation protein (FMRP). Previous reports have shown that CYFIP1 and CYFIP2 may play roles in posttranscriptional regulation in different ways. While CYFIP1 is involved in translation initiation via the 5′UTR, CYFIP2 may regulate mRNA expression via the 3′UTR. In addition, this CYFIP protein family is involved in neural development and maturation as well as in different neural disorders, such as intellectual disabilities, autistic spectrum disorders, and Alzheimer’s disease. In this review, we map diverse studies regarding the functions, regulation, and implications of CYFIP proteins in a series of molecular pathways. We also highlight mutations and their structural effects both in functional studies and in neural diseases.

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Notes

  1. For an overview on the WRC and actin dynamics, we suggest the following reviews: [32, 34, 74,75,76].

References

  1. Courchesne E, Pramparo T, Gazestani VH et al (2019) The ASD living biology: from cell proliferation to clinical phenotype. Mol Psychiatry 24:88–107. https://doi.org/10.1038/s41380-018-0056-y

    Article  PubMed  Google Scholar 

  2. Gataullina S, Bienvenu T, Nabbout R et al (2019) Gene mutations in pediatric epilepsies cause NMDA-pathy, and phasic and tonic GABA-pathy. Dev Med Child Neurol 61:891–898. https://doi.org/10.1111/dmcn.14152

    Article  PubMed  Google Scholar 

  3. Dark C, Homman-Ludiye J, Bryson-Richardson RJ (2018) The role of ADHD associated genes in neurodevelopment. Dev Biol 438:69–83. https://doi.org/10.1016/j.ydbio.2018.03.023

    Article  CAS  PubMed  Google Scholar 

  4. Zhuo C, Hou W, Li G et al (2019) The genomics of schizophrenia: shortcomings and solutions. Prog Neuropsychopharmacol Biol Psychiatry 93:71–76. https://doi.org/10.1016/j.pnpbp.2019.03.009

    Article  CAS  PubMed  Google Scholar 

  5. Gulisano W, Maugeri D, Baltrons MA et al (2018) Role of amyloid-β and tau proteins in Alzheimer’s disease: confuting the amyloid cascade. J Alzheimers Dis 64:S611–S631. https://doi.org/10.3233/JAD-179935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pourcain BS, Robinson EB, Antilla V et al (2018) ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties. Mol Psychiatry 23:263–270. https://doi.org/10.1038/mp.2016.198

    Article  Google Scholar 

  7. Noroozi R, Omrani MD, Sayad A et al (2018) Cytoplasmic FMRP interacting protein 1/2 (CYFIP1/2) expression analysis in autism. Metab Brain Dis 33:1353–1358. https://doi.org/10.1007/s11011-018-0249-8

    Article  CAS  PubMed  Google Scholar 

  8. Sayad A, Ranjbaran F, Ghafouri-Fard S et al (2018) Expression analysis of CYFIP1 and CAMKK2 genes in the blood of epileptic and schizophrenic patients. J Mol Neurosci 65:336–342. https://doi.org/10.1007/s12031-018-1106-2

    Article  CAS  PubMed  Google Scholar 

  9. Domínguez-Iturza N, Lo AC, Shah D et al (2019) The autism- and schizophrenia-associated protein CYFIP1 regulates bilateral brain connectivity and behaviour. Nat Commun 10:3454. https://doi.org/10.1038/s41467-019-11203-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Clifton NE, Thomas KL, Wilkinson LS et al (2020) FMRP and CYFIP1 at the synapse and their role in psychiatric vulnerability. Complex Psychiatry. https://doi.org/10.1159/000506858

    Article  PubMed  PubMed Central  Google Scholar 

  11. Waltes R, Freitag CM, Herlt T et al (2019) Impact of autism-associated genetic variants in interaction with environmental factors on ADHD comorbidities: an exploratory pilot study. J Neural Transm 126:1679–1693. https://doi.org/10.1007/s00702-019-02101-0

    Article  CAS  PubMed  Google Scholar 

  12. Tiwari SS, Mizuno K, Ghosh A et al (2016) Alzheimer-related decrease in CYFIP2 links amyloid production to tau hyperphosphorylation and memory loss. Brain 139:2751–2765. https://doi.org/10.1093/brain/aww205

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hoeffer CA, Sanchez E, Hagerman RJ et al (2012) Altered mTOR signaling and enhanced CYFIP2 expression levels in subjects with fragile X syndrome. Genes Brain Behav 11:332–341. https://doi.org/10.1111/j.1601-183X.2012.00768.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Han K, Chen H, Gennarino VA et al (2015) Fragile X-like behaviors and abnormal cortical dendritic spines in cytoplasmic FMR1-interacting protein 2-mutant mice. Hum Mol Genet 24:1813–1823. https://doi.org/10.1093/hmg/ddu595

    Article  CAS  PubMed  Google Scholar 

  15. Nakashima M, Kato M, Aoto K et al (2018) De novo hotspot variants in CYFIP2 cause early-onset epileptic encephalopathy. Ann Neurol 83:794–806. https://doi.org/10.1002/ana.25208

    Article  CAS  PubMed  Google Scholar 

  16. Kumar V, Kim K, Joseph C et al (2013) C57BL/6N mutation in cytoplasmic FMRP interacting protein 2 regulates cocaine response. Science 342:1508–1512. https://doi.org/10.1126/science.1245503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kirkpatrick SL, Goldberg LR, Yazdani N et al (2017) Cytoplasmic FMR1-interacting protein 2 is a major genetic factor underlying binge eating. Biol Psychiatry 81:757–769. https://doi.org/10.1016/j.biopsych.2016.10.021

    Article  CAS  PubMed  Google Scholar 

  18. Zhang Y, Kang Hyae R, Lee SH et al (2020) Enhanced prefrontal neuronal activity and social dominance behavior in postnatal forebrain excitatory neuron-specific Cyfip2 knock-out mice. Front Mol Neurosci 13:1–10. https://doi.org/10.3389/fnmol.2020.574947

    Article  CAS  Google Scholar 

  19. Kobayashi K, Kuroda S, Fukata M et al (1998) p140Sra-1 (specifically Rac1-associated protein) is a novel specific target for Rac1 small GTPase. J Biol Chem 273:291–295. https://doi.org/10.1074/jbc.273.1.291

    Article  CAS  PubMed  Google Scholar 

  20. Zhang Y, Kang H, Lee Y et al (2019) Smaller body size, early postnatal lethality, and cortical extracellular matrix-related gene expression changes of Cyfip2-null embryonic mice. Front Mol Neurosci 11:482. https://doi.org/10.3389/fnmol.2018.00482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Schenck A, Bardoni B, Moro A et al (2001) 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. Proc Natl Acad Sci USA 98:8844–8849. https://doi.org/10.1073/pnas.151231598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Abekhoukh S, Bardoni B (2014) CYFIP family proteins between autism and intellectual disability: links with Fragile X syndrome. Front Cell Neurosci. https://doi.org/10.3389/fncel.2014.00081

    Article  PubMed  PubMed Central  Google Scholar 

  23. Schaks M, Reinke M, Witke W, Rottner K (2020) Molecular dissection of neurodevelopmental disorder-causing mutations in CYFIP2. Cells 9:1355. https://doi.org/10.3390/cells9061355

    Article  CAS  PubMed Central  Google Scholar 

  24. Zhang Y, Kang HR, Han K (2019) Differential cell-type-expression of CYFIP1 and CYFIP2 in the adult mouse hippocampus. Anim Cells Syst 23:380–383. https://doi.org/10.1080/19768354.2019.1696406

    Article  CAS  Google Scholar 

  25. Cioni J-M, Wong HH-W, Bressan D et al (2018) Axon–axon interactions regulate topographic optic tract sorting via CYFIP2-dependent WAVE complex function. Neuron 97:1078-1093.e6. https://doi.org/10.1016/j.neuron.2018.01.027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Didsbury J, Evans T, Snyderman R (1989) Rac, a novel ras-related family of proteins that are botulinum toxin substrates. J Biol Chem 264:5

    Article  Google Scholar 

  27. Abo A, Pick E, Hall A et al (1991) Activation of the NADPH oxidase involves the small GTP-binding protein p21rac1. Nature 353:668–670

    Article  CAS  PubMed  Google Scholar 

  28. Kim SK (2000) Cell polarity: new PARtners for Cdc42 and Rac. Nat Cell Biol 2:E143–E145. https://doi.org/10.1038/35019623

    Article  CAS  PubMed  Google Scholar 

  29. Castilho RM, Squarize CH, Patel V et al (2007) Requirement of Rac1 distinguishes follicular from interfollicular epithelial stem cells. Oncogene 26:5078–5085. https://doi.org/10.1038/sj.onc.1210322

    Article  CAS  PubMed  Google Scholar 

  30. Guo F, Cancelas JA, Hildeman D et al (2008) Rac GTPase isoforms Rac1 and Rac2 play a redundant and crucial role in T-cell development. Blood 112:1767–1775. https://doi.org/10.1182/blood-2008-01-132068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ridley AJ, Paterson HF, Johnston CL et al (1992) The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 70:401–410

    Article  CAS  PubMed  Google Scholar 

  32. Takenawa T, Suetsugu S (2007) The WASP–WAVE protein network: connecting the membrane to the cytoskeleton. Nat Rev Mol Cell Biol 8:37–48. https://doi.org/10.1038/nrm2069

    Article  CAS  PubMed  Google Scholar 

  33. Innocenti M, Zucconi A, Disanza A et al (2004) Abi1 is essential for the formation and activation of a WAVE2 signalling complex. Nat Cell Biol 6:319–327. https://doi.org/10.1038/ncb1105

    Article  CAS  PubMed  Google Scholar 

  34. Campellone KG, Welch MD (2010) A nucleator arms race: cellular control of actin assembly. Nat Rev Mol Cell Biol 11:237–251. https://doi.org/10.1038/nrm2867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Abekhoukh S, Sahin HB, Grossi M et al (2017) New insights into the regulatory function of CYFIP1 in the context of WAVE- and FMRP-containing complexes. Dis Model Mech 10:463–474. https://doi.org/10.1242/dmm.025809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Fricano-Kugler C, Gordon A, Shin G et al (2019) CYFIP1 overexpression increases fear response in mice but does not affect social or repetitive behavioral phenotypes. Mol Autism 10:25. https://doi.org/10.1186/s13229-019-0278-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Verkerk AJMH, Pieretti M, Sutcliffe JS et al (1991) Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65:905–914. https://doi.org/10.1016/0092-8674(91)90397-H

    Article  CAS  PubMed  Google Scholar 

  38. Bagni C, Oostra BA (2013) Fragile X syndrome: from protein function to therapy. Am J Med Genet A 161A:2809–2821. https://doi.org/10.1002/ajmg.a.36241

    Article  CAS  PubMed  Google Scholar 

  39. Michaelsen-Preusse K, Feuge J, Korte M (2018) Imbalance of synaptic actin dynamics as a key to fragile X syndrome? J Physiol 596:2773–2782. https://doi.org/10.1113/JP275571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Napoli I, Mercaldo V, Boyl PP et al (2008) The fragile X syndrome protein Represses Activity-Dependent Translation through CYFIP1, a New 4E-BP. Cell 134:1042–1054. https://doi.org/10.1016/j.cell.2008.07.031

    Article  CAS  PubMed  Google Scholar 

  41. De Rubeis S, Pasciuto E, Li KW et al (2013) CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic spine formation. Neuron 79:1169–1182. https://doi.org/10.1016/j.neuron.2013.06.039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Di Marino D, D’Annessa I, Tancredi H et al (2015) A unique binding mode of the eukaryotic translation initiation factor 4E for guiding the design of novel peptide inhibitors: Cyfip1 and eIF4E Inhibitor Peptides. Protein Sci 24:1370–1382. https://doi.org/10.1002/pro.2708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hsiao K, Harony-Nicolas H, Buxbaum JD et al (2016) Cyfip1 regulates presynaptic activity during development. J Neurosci 36:1564–1576. https://doi.org/10.1523/JNEUROSCI.0511-15.2016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Oguro-Ando A, Rosensweig C, Herman E et al (2015) Increased CYFIP1 dosage alters cellular and dendritic morphology and dysregulates mTOR. Mol Psychiatry 20:1069–1078. https://doi.org/10.1038/mp.2014.124

    Article  CAS  PubMed  Google Scholar 

  45. Sahasrabudhe A, Begum F, Guevara C et al (2021) Cyfip1 regulates SynGAP1 at hippocampal synapses. Front Synaptic Neurosci 12:581714. https://doi.org/10.3389/fnsyn.2020.581714

    Article  PubMed  PubMed Central  Google Scholar 

  46. Shen W, Jin L, Zhu A et al (2021) Treadmill exercise enhances synaptic plasticity in the ischemic penumbra of MCAO mice by inducing the expression of Camk2a via CYFIP1 upregulation. Life Sci 270:119033. https://doi.org/10.1016/j.lfs.2021.119033

    Article  CAS  PubMed  Google Scholar 

  47. Kawano Y, Yoshimura T, Tsuboi D et al (2005) CRMP-2 is involved in kinesin-1-dependent transport of the sra-1/WAVE1 complex and axon formation. Mol Cell Biol 25:9920–9935. https://doi.org/10.1128/MCB.25.22.9920-9935.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Dziunycz PJ, Neu J, Lefort K et al (2017) CYFIP1 is directly controlled by NOTCH1 and down-regulated in cutaneous squamous cell carcinoma. PLoS ONE 12:e0173000. https://doi.org/10.1371/journal.pone.0173000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Habela CW, Yoon K-J, Kim N-S et al (2020) Persistent Cyfip1 expression is required to maintain the adult subventricular zone neurogenic niche. J Neurosci 40:2015–2024. https://doi.org/10.1523/JNEUROSCI.2249-19.2020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Egger B, Gold KS, Brand AH (2010) Notch regulates the switch from symmetric to asymmetric neural stem cell division in the Drosophila optic lobe. Development 137:2981–2987. https://doi.org/10.1242/dev.051250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Contreras EG, Egger B, Gold KS, Brand AH (2018) Dynamic Notch signalling regulates neural stem cell state progression in the Drosophila optic lobe. Neural Dev 13:25. https://doi.org/10.1186/s13064-018-0123-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ghosh A, Mizuno K, Tiwari SS et al (2020) Alzheimer’s disease-related dysregulation of mRNA translation causes key pathological features with ageing. Transl Psychiatry 10:192. https://doi.org/10.1038/s41398-020-00882-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Darnell JC, Van Driesche SJ, Zhang C et al (2011) FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 146:247–261. https://doi.org/10.1016/j.cell.2011.06.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lee Y, Zhang Y, Kang H et al (2020) Epilepsy- and intellectual disability-associated CYFIP2 interacts with both actin regulators and RNA-binding proteins in the neonatal mouse forebrain. Biochem Biophys Res Commun 529:1–6. https://doi.org/10.1016/j.bbrc.2020.05.221

    Article  CAS  PubMed  Google Scholar 

  55. Lin J, Liao S, Li E et al (2020) circCYFIP2 acts as a sponge of miR-1205 and affects the expression of its target gene E2F1 to regulate gastric cancer metastasis. Mol Ther Nucleic Acids 21:121–132. https://doi.org/10.1016/j.omtn.2020.05.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Liu Y, Liu H, Bian Q (2020) Identification of potential biomarkers associated with basal cell carcinoma. BioMed Res Int 2020:1–10. https://doi.org/10.1155/2020/2073690

    Article  CAS  Google Scholar 

  57. May P, May E (1999) Twenty years of p53 research: structural and functional aspects of the p53 protein. Oncogene 18:7621–7636. https://doi.org/10.1038/sj.onc.1203285

    Article  CAS  PubMed  Google Scholar 

  58. Jackson RS, Cho Y-J, Stein S, Liang P (2007) CYFIP2, a direct p53 target, is leptomycin-B sensitive. Cell Cycle 6:95–103. https://doi.org/10.4161/cc.6.1.3665

    Article  CAS  PubMed  Google Scholar 

  59. Ozaki T, Nakagawara A (2011) Role of p53 in cell death and human cancers. Cancers 3:994–1013. https://doi.org/10.3390/cancers3010994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Mayne M, Moffatt T, Kong H et al (2004) CYFIP2 is highly abundant in CD4+ cells from multiple sclerosis patients and is involved in T cell adhesion. Eur J Immunol 34:1217–1227. https://doi.org/10.1002/eji.200324726

    Article  CAS  PubMed  Google Scholar 

  61. Levanon EY, Halleger M, Kinar Y et al (2005) Evolutionarily conserved human targets of adenosine to inosine RNA editing. Nucleic Acids Res 33:1162–1168. https://doi.org/10.1093/nar/gki239

    Article  PubMed  PubMed Central  Google Scholar 

  62. Nishimoto Y, Yamashita T, Hideyama T et al (2008) Determination of editors at the novel A-to-I editing positions. Neurosci Res 61:201–206. https://doi.org/10.1016/j.neures.2008.02.009

    Article  CAS  PubMed  Google Scholar 

  63. Kwak S, Nishimoto Y, Yamashita T (2008) Newly identified ADAR-mediated A-to-I editing positions as a tool for ALS research. RNA Biol 5:193–197. https://doi.org/10.4161/rna.6925

    Article  CAS  PubMed  Google Scholar 

  64. Wahlstedt H, Daniel C, Enstero M, Ohman M (2009) Large-scale mRNA sequencing determines global regulation of RNA editing during brain development. Genome Res 19:978–986. https://doi.org/10.1101/gr.089409.108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Levitsky LI, Kliuchnikova AA, Kuznetsova KG et al (2019) Adenosine-to-inosine RNA editing in mouse and human brain proteomes. Proteomics 19:1900195. https://doi.org/10.1002/pmic.201900195

    Article  CAS  Google Scholar 

  66. Shtrichman R, Germanguz I, Mandel R et al (2012) Altered A-to-I RNA editing in human embryogenesis. PLoS ONE 7:e41576. https://doi.org/10.1371/journal.pone.0041576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Nicholas A, de Magalhaes JP, Kraytsberg Y et al (2010) Age-related gene-specific changes of A-to-I mRNA editing in the human brain. Mech Ageing Dev 131:445–447. https://doi.org/10.1016/j.mad.2010.06.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Bonini D, Filippini A, La Via L et al (2015) Chronic glutamate treatment selectively modulates AMPA RNA editing and ADAR expression and activity in primary cortical neurons. RNA Biol 12:43–53. https://doi.org/10.1080/15476286.2015.1008365

    Article  PubMed  PubMed Central  Google Scholar 

  69. Eden S, Rohatgi R, Podtelejnikov AV et al (2002) Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature 418:790–793. https://doi.org/10.1038/nature00859

    Article  CAS  PubMed  Google Scholar 

  70. Derivery E, Lombard B, Loew D, Gautreau A (2009) The Wave complex is intrinsically inactive. Cell Motil Cytoskelet 66:777–790. https://doi.org/10.1002/cm.20342

    Article  CAS  Google Scholar 

  71. Gautreau A, Ho H, Li J et al (2004) Purification and architecture of the ubiquitous Wave complex. PNAS 101:4379–4383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Chen Z, Borek D, Padrick SB et al (2010) Structure and control of the actin regulatory WAVE complex. Nature 468:533–538. https://doi.org/10.1038/nature09623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Lebensohn AM, Kirshner MW (2009) Activation of the WAVE complex by coincident signals controls actin assembly. Mol Cell 36:512–524. https://doi.org/10.1016/j.molcel.2009.10.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Takahashi K (2012) WAVE2 protein complex coupled to membrane and microtubules. J Oncol. https://doi.org/10.1155/2012/590531

    Article  PubMed  PubMed Central  Google Scholar 

  75. Svitkina T (2018) The actin cytoskeleton and actin-based motility. Cold Spring Harb Perspect Biol 10:a018267. https://doi.org/10.1101/cshperspect.a018267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Rottner K, Schaks M (2019) Assembling actin filaments for protrusion. Curr Opin Cell Biol 56:53–63. https://doi.org/10.1016/j.ceb.2018.09.004

    Article  CAS  PubMed  Google Scholar 

  77. Schaks M, Singh SP, Kage F et al (2018) Distinct interaction sites of Rac GTPase with WAVE regulatory complex have non-redundant functions in vivo. Curr Biol 28:3674-3684.e6. https://doi.org/10.1016/j.cub.2018.10.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Chen B, Chou H-T, Brautigam CA et al (2017) Rac1 GTPase activates the WAVE regulatory complex through two distinct binding sites. Elife 6:1–22. https://doi.org/10.7554/eLife.29795

    Article  Google Scholar 

  79. Lee Y, Kim D, Ryu JR et al (2017) 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 28:749–754

    Article  CAS  PubMed  Google Scholar 

  80. Marsden KC, Jain RA, Wolman MA et al (2018) A Cyfip2-dependent excitatory interneuron pathway establishes the innate startle threshold. Cell Rep 23:878–887. https://doi.org/10.1016/j.celrep.2018.03.095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Konietzny A, Bär J, Mikhaylova M (2017) Dendritic actin cytoskeleton: structure, functions, and regulations. Front Cell Neurosci 11:147. https://doi.org/10.3389/fncel.2017.00147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Alvarez VA, Sabatini BL (2007) Anatomical and physiological plasticity of dendritic spines. Annu Rev Neurosci 30:79–97. https://doi.org/10.1146/annurev.neuro.30.051606.094222

    Article  CAS  PubMed  Google Scholar 

  83. Koseki K, Taniguchi D, Yamashiro S et al (2019) Lamellipodium tip actin barbed ends serve as a force sensor. Genes Cells 24:705–718. https://doi.org/10.1111/gtc.12720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Pathania M, Davenport EC, Muir J et al (2014) The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines. Transl Psychiatry 4:e374–e374. https://doi.org/10.1038/tp.2014.16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Kulkarni VA, Firestein BL (2012) The dendritic tree and brain disorders. Mol Cell Neurosci 50:10–20. https://doi.org/10.1016/j.mcn.2012.03.005

    Article  CAS  PubMed  Google Scholar 

  86. Sledziowska M, Kalbassi S, Baudouin SJ (2020) Complex interactions between genes and social environment cause phenotypes associated with autism spectrum disorders in mice. eNeuro 7:1–15. https://doi.org/10.1523/ENEURO.0124-20.2020

    Article  Google Scholar 

  87. Butler MG (2017) Clinical and genetic aspects of the 15q11.2 BP1-BP2 microdeletion disorder: 15q11.2 BP1-BP2 microdeletion. J Intellect Disabil Res 61:568–579. https://doi.org/10.1111/jir.12382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Silva AI, Haddon JE, Ahmed Syed Y et al (2019) Cyfip1 haploinsufficient rats show white matter changes, myelin thinning, abnormal oligodendrocytes and behavioural inflexibility. Nat Commun 10:3455. https://doi.org/10.1038/s41467-019-11119-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Zuchero JB, Fu M, Sloan SA et al (2015) CNS myelin wrapping is driven by actin disassembly. Dev Cell 34:152–167. https://doi.org/10.1016/j.devcel.2015.06.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Babbs RK, Beierle JA, Ruan QT et al (2019) Cyfip1 haploinsufficiency increases compulsive-like behavior and modulates palatable food intake in mice: dependence on Cyfip2 genetic background, parent-of origin, and sex. Genes Genet Genome 9:3009–3022. https://doi.org/10.1534/g3.119.400470

    Article  CAS  Google Scholar 

  91. Faye MD, Graber TE, Holcik M (2014) Assessment of selective mRNA translation in mammalian cells by polysome profiling. J Vis Exp 92:e52295. https://doi.org/10.3791/52295

    Article  CAS  Google Scholar 

  92. Kim GH, Zhang Y, Kang HR (2020) Altered presynaptic function and number of mitochondria in the medial prefrontal cortex of adult Cyfip2 heterozygous mice. Mol Brain 13:123. https://doi.org/10.1186/s13041-020-00668-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Hoover BR, Reed MN, Su J et al (2010) Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration. Neuron 68:1067–1081. https://doi.org/10.1016/j.neuron.2010.11.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Islam T (2016) Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol Res 39:73–82. https://doi.org/10.1080/01616412.2016.1251711

    Article  CAS  PubMed  Google Scholar 

  95. Peng J, Wang Y, He F et al (2018) Novel West syndrome candidate genes in a Chinese cohort. CNS Neurosci Ther 24:1196–1206. https://doi.org/10.1111/cns.12860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Zweier M, Begemann A, McWalter K et al (2019) Spatially clustering de novo variants in CYFIP2, encoding the cytoplasmic FMRP interacting protein 2, cause intellectual disability and seizures. Eur J Hum Genet 27:747–759. https://doi.org/10.1038/s41431-018-0331-z

    Article  PubMed  PubMed Central  Google Scholar 

  97. Zhong M, Liao S, Li T et al (2019) Early diagnosis improving the outcome of an infant with epileptic encephalopathy with cytoplasmic FMRP interacting protein 2 mutation: case report and literature review. Medicine (Baltimore) 98:e17749. https://doi.org/10.1097/MD.0000000000017749

    Article  Google Scholar 

  98. Begeman A, Sticht H, Begtrup A et al (2020) New insights into the clinical and molecular spectrum of the novel CYFIP2-related neurodevelopmental disorder and impairment of the WRC-mediated actin dynamics. Genet Med 23:543–554. https://doi.org/10.1038/s41436-020-01011-x

    Article  CAS  Google Scholar 

  99. Zhang Y, Lee Y, Han K (2019) Neuronal function and dysfunction of CYFIP2: from actin dynamics to early infantile epileptic encephalopathy. BMB Rep 52:304–311. https://doi.org/10.5483/BMBRep.2019.52.5.097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Lee SH, Zhang Y, Park J et al (2020) Haploinsufficiency of Cyfip2 causes lithium-responsive prefrontal dysfunction. Ann Neurol 00:1–18. https://doi.org/10.1002/ana.25827

    Article  CAS  Google Scholar 

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Funding

CNPq/Instituto Carlos Chagas Nº 15/2019—PROEP/ICC—442324/2019-7.

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Author notes

  1. Ísis Venturi Biembengut and Isabelle Leticia Zaboroski Silva contributed equally to this work.

Authors and Affiliations

  1. Carlos Chagas Institute—FIOCRUZ-PR, Rua Prof. Algacyr Munhoz Mader, 3775, CIC, Curitiba, Paraná, 81830-010, Brazil

    Ísis Venturi Biembengut, Isabelle Leticia Zaboroski Silva, Tatiana de Arruda Campos Brasil de Souza & Patrícia Shigunov

Authors
  1. Ísis Venturi Biembengut
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  2. Isabelle Leticia Zaboroski Silva
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  3. Tatiana de Arruda Campos Brasil de Souza
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  4. Patrícia Shigunov
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Contributions

ÍVB and ILZS contributed to the study conception and design, performed the literature search, and wrote the original manuscript. PS and TACBS critically revised the work. All authors read and approved the final manuscript.

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Correspondence to Patrícia Shigunov.

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Biembengut, Í.V., Silva, I.L.Z., Souza, T.d.A.C.B.d. et al. Cytoplasmic FMR1 interacting protein (CYFIP) family members and their function in neural development and disorders. Mol Biol Rep 48, 6131–6143 (2021). https://doi.org/10.1007/s11033-021-06585-6

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  • DOI: https://doi.org/10.1007/s11033-021-06585-6

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