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Legumain Functions as a Transient TrkB Sheddase
Christoph Holzner1, Katharina Böttinger1, Constantin Blöchl1
1Department of Biosciences and Medical Biology, University of Salzburg, Hellbrunner Str. 34, A-5020 Salzburg, Austria.
International Journal of Molecular Sciences
|March 29, 2023
Summary
The cysteine protease legumain processes the TrkB receptor ectodomain, potentially scavenging BDNF. This reveals a new link between TrkB signaling and legumain activity, relevant for neurodegeneration.
Area of Science:
- Molecular biology
- Neuroscience
- Cell biology
Background:
- Legumain, a cysteine protease, is typically in endo-lysosomal compartments but can reach the cell surface via integrin αVβ3.
- Legumain expression is known to be inversely correlated with Brain-Derived Neurotrophic Factor (BDNF)-Tropomyosin receptor kinase B (TrkB) activity.
Purpose of the Study:
- To investigate the direct interaction between legumain and the TrkB receptor.
- To elucidate the mechanism by which legumain influences TrkB-BDNF signaling.
Main Methods:
- In vitro processing assays using purified legumain and TrkB ectodomain.
- Analysis of TrkB cleavage products and their ability to bind BDNF.
Main Results:
- Legumain cleaves the C-terminal linker region of the TrkB ectodomain in vitro.
- TrkB bound to BDNF is resistant to legumain cleavage.
- Legumain-processed TrkB retains its capacity to bind BDNF, suggesting a soluble scavenger function.
Conclusions:
- Legumain directly processes the TrkB ectodomain, adding a new layer to the regulation of BDNF-TrkB signaling.
- This processing may generate soluble TrkB fragments that act as decoys for BDNF.
- The findings provide a mechanistic link between legumain activity and neurodegenerative processes.
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