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Published on: July 11, 2020
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SPIG1 negatively regulates BDNF maturation.
Ryoko Suzuki1, Masahito Matsumoto, Akihiro Fujikawa
1Division of Molecular Neurobiology, National Institute for Basic Biology, and School of Life Science, Graduate University for Advanced Studies, Okazaki, Aichi 444-8787, Japan.
Summary
SPIG1 (Follistatin-like protein 4) negatively regulates brain-derived neurotrophic factor (BDNF) maturation. This suppression of BDNF reduces axonal branching and spine formation in developing neurons.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- SPIG1 (Follistatin-like protein 4) is a dorsal-retina-specific molecule.
- Axon guidance and targeting are crucial for neural circuit formation.
Purpose of the Study:
- To investigate the function of SPIG1 in retinal ganglion cell (RGC) axon development.
- To elucidate the molecular mechanism by which SPIG1 influences neural development.
Main Methods:
- SPIG1 knockdown in chick embryo RGCs.
- In vitro axon branching assays with BDNF neutralizing antibodies.
- Co-localization and binding assays of SPIG1 with proBDNF and mature BDNF.
- Analysis of BDNF, TrkB, and spine density in SPIG1-knockout mice hippocampus.
Main Results:
- SPIG1 knockdown in RGCs caused ectopic axon branching and failed tectal targeting.
- SPIG1 knockdown enhanced in vitro axon branching, which was blocked by anti-BDNF antibody.
- SPIG1 directly binds to proBDNF, inhibiting mature BDNF secretion.
- SPIG1 knockout mice showed increased mature BDNF, p-TrkB, and hippocampal spine density.
Conclusions:
- SPIG1 negatively regulates BDNF maturation by interacting with proBDNF.
- This interaction suppresses RGC axonal branching and spine formation.
- SPIG1 plays a critical role in controlling neural circuit development through BDNF pathway modulation.
