Local F-actin Network Links Synapse Formation and Axon Branching
Open accessAbstract
Axonal branching and synapse formation are tightly linked developmental events during the establishment of synaptic circuits. Newly formed synapses promote branch initiation and stability. However, little is known about molecular mechanisms that link these two processes. Here, we show that local assembly of an F-actin cytoskeleton at nascent presynaptic sites initiates both synapse formation and axon branching. We further find that assembly of the F-actin network requires a direct interaction between the synaptic cell adhesion molecule SYG-1 and a key regulator of actin cytoskeleton, the WVE-1/WAVE regulatory complex (WRC). SYG-1 cytoplasmic tail binds to the WRC using a consensus WRC interacting receptor sequence (WIRS). WRC mutants or mutating the SYG-1 WIRS motif leads to loss of local F-actin, synaptic material, and axonal branches. Together, these data suggest that synaptic adhesion molecules, which serve as a necessary component for both synaptogenesis and axonal branch formation, directly regulate subcellular actin cytoskeletal organization.
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In C. elegans, SYG-1, an adhesion molecule, interacts with the WAVE complex through the WIRS motif, and this interaction is required for synaptic F-actin dynamics, synapse formation and axon branching.
“For example, in C. elegans, SYG-1, an adhesion molecule, interacts with the WAVE complex through the WIRS motif, and this interaction is required for synaptic F-actin dynamics, synapse formation and axon branching55.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [55]
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The WAVE complex in developmental and adulthood brain disorders
Kim, H.-G., Berdasco, C., Nairn, A. C., & Kim, Y. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01386-w · Cited by 8 · see citing works
- Authors
- Chia, P. H., Chen, B., Li, P., Rosen, M. K., & Shen, K.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Shen, Kang
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 156
- Issue
- 1-2
- Pages
- 208-220
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3954643
- OpenAlex
- W2077922474
- Cited by
- 145
- References
- 0
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 9 · 2023: 7 · 2022: 13 · 2021: 15 · 2020: 11 · 2019: 11 · 2018: 12 · 2017: 11 · 2016: 13 · 2015: 19 · 2014: 11
- FWCI
- 7.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute of Mental Health (T32MH020016)
- National Institute of General Medical Sciences (R01GM056322)
- National Institute of Neurological Disorders and Stroke (R37NS048392, R01NS048392)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- F-actin cytoskeleton, synaptogenesis, axon branching, WAVE regulatory complex, synaptic adhesion molecules, Caenorhabditis elegans
- MeSH terms
- Actins, Amino Acid Sequence, Animals, Axons, Immunoglobulins, Molecular Sequence Data, Synapses, Sequence Alignment, Caenorhabditis elegans, Amino Acid Motifs, Caenorhabditis elegans Proteins, Multiprotein Complexes, Neurogenesis
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