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Drosophila cyfip Regulates Synaptic Development and Endocytosis by Suppressing Filamentous Actin Assembly

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Zhao, Lu, Wang, Dan, Wang, Qifu, Rodal, Avital A., Zhang, Yong Q.·2013·PLoS Genetics
DOI 10.1371/journal.pgen.1003450PMC PMC3616907
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Abstract

The formation of synapses and the proper construction of neural circuits depend on signaling pathways that regulate cytoskeletal structure and dynamics. After the mutual recognition of a growing axon and its target, multiple signaling pathways are activated that regulate cytoskeletal dynamics to determine the morphology and strength of the connection. By analyzing Drosophila mutations in the cytoplasmic FMRP interacting protein Cyfip, we demonstrate that this component of the WAVE complex inhibits the assembly of filamentous actin (F-actin) and thereby regulates key aspects of synaptogenesis. Cyfip regulates the distribution of F-actin filaments in presynaptic neuromuscular junction (NMJ) terminals. At cyfip mutant NMJs, F-actin assembly was accelerated, resulting in shorter NMJs, more numerous satellite boutons, and reduced quantal content. Increased synaptic vesicle size and failure to maintain excitatory junctional potential amplitudes under high-frequency stimulation in cyfip mutants indicated an endocytic defect. cyfip mutants exhibited upregulated bone morphogenetic protein (BMP) signaling, a major growth-promoting pathway known to be attenuated by endocytosis at the Drosophila NMJ. We propose that Cyfip regulates synapse development and endocytosis by inhibiting actin assembly.

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  • A role for CYFIP1 in the regulation of Rac1-dependent F-actin assembly in Drosophila NMJ presynaptic terminals has been demonstrated, where it is important for synaptogenesis and presynaptic quantal content.

    “A role for CYFIP1 in the regulation of Rac1-dependent F-actin assembly in Drosophila NMJ presynaptic terminals was also recently demonstrated, where it was shown to be important for synaptogenesis and presynaptic quantal content.51,52”

    From The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines (2014) · cites this paper as [51]

    The Abstract and Results report altered F-actin assembly and synaptic development at Drosophila NMJs, along with reduced quantal content in cyfip mutants. But the Introduction says the Rac1-to-WAVE mechanism had been demonstrated only in vitro; this paper does not demonstrate that the NMJ effects are Rac1-dependent. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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Cited by

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Authors
Zhao, L., Wang, D., Wang, Q., Rodal, A. A., & Zhang, Y. Q.
Affiliations
  • Chinese Academy of Sciences (CN)
  • Brandeis University (US)
ORCID
Venue
PLoS Genetics
Publisher
Public Library of Science (PLoS)
Published
2013-04-04
Volume
9
Issue
4
Pages
e1003450
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
DOI
10.1371/journal.pgen.1003450
PMC
PMC3616907
OpenAlex
W1963837195
Cited by
67
References
4
Citations by year
2026: 3 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 7 · 2020: 8 · 2019: 8 · 2018: 1 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 10 · 2013: 2
FWCI
3.60
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Genetics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Brandeis Institutional Repository (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Natural Science Foundation of China (31000487, 30930033, 30871388)
  • Chinese Academy of Sciences (XDB02020400)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
Keywords
FMRP, WAVE complex, actin filament assembly, synaptogenesis, synaptic vesicle endocytosis, neuromuscular junction, presynaptic terminals, quantal content, BMP signaling, Drosophila
MeSH terms
Actins, Animals, Cytoskeleton, Drosophila melanogaster, Mutation, Neuromuscular Junction, Synapses, Signal Transduction, Bone Morphogenetic Proteins, Drosophila Proteins, Adaptor Proteins, Signal Transducing

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