ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
Cyfip1 Regulates Presynaptic Activity during Development.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2023Pooled it
- PQBP1-dependent alternative RNA splicing underlies high calorie diet-induced cognitive impairment.Molecular psychiatry · 2026Article
- Fatty acid amide hydrolase inhibition for treatment of amyotrophic lateral sclerosis.JCI insight · 2026Article
- 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 · 2026Article
- CYFIP1 governs the development of cortical axons by modulating calcium availability.Nature communications · 2025Article
- Altered development and network connectivity in a human neuronal model of 15q11.2 deletion-related neurodevelopmental disorders.Translational psychiatry · 2025Article
- Impact of Genetic Variants Associated with Neurodevelopmental Disorders on the WAVE Regulatory Complex.Journal of chemical information and modeling · 2025Article
- The Unified Theory of Neurodegeneration Pathogenesis Based on Axon Deamidation.International journal of molecular sciences · 2025Review
- The WAVE complex in developmental and adulthood brain disorders.Experimental & molecular medicine · 2025Review
- Molecular basis of the CYFIP2 and NCKAP1 autism-linked variants in the WAVE regulatory complex.Protein science : a publication of the Protein Society · 2025Article
- Integrated machine learning-driven disulfidptosis profiling: CYFIP1 and EMILIN1 as therapeutic nodes in neuroblastoma.Journal of cancer research and clinical oncology · 2024Article
- Orchestration of synaptic functions by WAVE regulatory complex-mediated actin reorganization.Experimental & molecular medicine · 2023Review
- Hypoxic Preconditioned Neural Stem Cell-Derived Extracellular Vesicles Contain Distinct Protein Cargo from Their Normal Counterparts.Current issues in molecular biology · 2023Article
- Long-term functional regeneration of radiation-damaged salivary glands through delivery of a neurogenic hydrogel.Science advances · 2022Article
- FMRP Sustains Presynaptic Function via Control of Activity-Dependent Bulk Endocytosis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Cytoplasmic FMR1 interacting protein (CYFIP) family members and their function in neural development and disorders.Molecular biology reports · 2021Review
- Haploinsufficiency of the schizophrenia and autism risk gene Cyfip1 causes abnormal postnatal hippocampal neurogenesis through microglial and Arp2/3 mediated actin dependent mechanisms.Translational psychiatry · 2021Article
- DNA methylation differences at birth after conception through ART.Human reproduction (Oxford, England) · 2021Article
- FMRP and CYFIP1 at the Synapse and Their Role in Psychiatric Vulnerability.Complex psychiatry · 2020Review
- Altered presynaptic function and number of mitochondria in the medial prefrontal cortex of adult Cyfip2 heterozygous mice.Molecular brain · 2020Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Copy number variations encompassing the gene encoding Cyfip1 have been associated with a variety of human diseases, including autism and schizophrenia. Here we show that juvenile mice hemizygous for Cyfip1 have altered presynaptic function, enhanced protein translation, and increased levels of F-actin. In developing hippocampus, reduced Cyfip1 levels serve to decrease paired pulse facilitation and increase miniature EPSC frequency without a change in amplitude. Higher-resolution examination shows these changes to be caused primarily by an increase in presynaptic terminal size and enhanced vesicle release probability. Short hairpin-mediated knockdown of Cyfip1 coupled with expression of mutant Cyfip1 proteins indicates that the presynaptic alterations are caused by dysregulation of the WAVE regulatory complex. Such dysregulation occurs downstream of Rac1 as acute exposure to Rac1 inhibitors rescues presynaptic responses in culture and in hippocampal slices. The data serve to highlight an early and essential role for Cyfip1 in the generation of normally functioning synapses and suggest a means by which changes in Cyfip1 levels could impact the generation of neural networks and contribute to abnormal and maladaptive behaviors. SIGNIFICANCE STATEMENT: Several developmental brain disorders have been associated with gene duplications and deletions that serve to increase or decrease levels of encoded proteins. Cyfip1 is one such protein, but the role it plays in brain development is poorly understood. We asked whether decreased Cyfip1 levels altered the function of developing synapses. The data show that synapses with reduced Cyfip1 are larger and release neurotransmitter more rapidly. These effects are due to Cyfip1's role in actin polymerization and are reversed by expression of a Cyfip1 mutant protein retaining actin regulatory function or by inhibiting Rac1. Thus, Cyfip1 has a more prominent early role regulating presynaptic activity during a stage of development when activity helps to define neural pathways.
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Registered trials
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.