Legumain Functions as a Transient TrkB Sheddase.

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.

Citation

Christoph Holzner, Katharina Böttinger, Constantin Blöchl, Christian G Huber, Sven O Dahms, Elfriede Dall, Hans Brandstetter. Legumain Functions as a Transient TrkB Sheddase. International journal of molecular sciences. 2023 Mar 11;24(6)

Mesh Tags

Substances

PMID: 36982466

search → result