IJMS, Vol. 24, Pages 5394: Legumain Functions as a Transient TrkB Sheddase

IJMS, Vol. 24, Pages 5394: Legumain Functions as a Transient TrkB Sheddase

International Journal of Molecular Sciences doi: 10.3390/ijms24065394

Authors: Christoph Holzner Katharina Böttinger Constantin Blöchl Christian G. Huber Sven O. Dahms Elfriede Dall Hans Brandstetter

While primarily found in endo-lysosomal compartments, the cysteine protease legumain can also translocate to the cell surface if stabilized by the interaction with the RGD-dependent integrin receptor αVβ3. Previously, it has been shown that legumain expression is inversely related to BDNF-TrkB activity. Here we show that legumain can conversely act on TrkB-BDNF by processing the C-terminal linker region of the TrkB ectodomain in vitro. Importantly, when in complex with BDNF, TrkB was not cleaved by legumain. Legumain-processed TrkB was still able to bind BDNF, suggesting a potential scavenger function of soluble TrkB towards BDNF. The work thus presents another mechanistic link explaining the reciprocal TrkB signaling and δ-secretase activity of legumain, with relevance for neurodegeneration.