Project P7: Beckinger / Bickenbach / Voss
Meprin β proteolytic activity and its regulation in the Golgi apparatus and the secretory pathway
Research team:
Silje Beckinger, Kira Bickenbach, Matthias Voss, Emily Charlotte Heßler
Objectives
The metalloprotease meprin β is of critical importance in the gastrointestinal tract and its dysregulation is implicated in colorectal cancer. It is synthesized as an inactive membrane protein precursor and its activation is attributed to tryptic cell-surface proteases or proteases in the extracellular space. However, novel preliminary degradome data have revealed meprin β-dependent proteolytic processing of in particular Golgi-resident proteins warranting an in-depth dissection of the dynamics and molecular mechanisms governing intracellular meprin β trafficking, its activation and activity as well as its interplay with other proteases implicated in protein processing in the Golgi such as SPPL3.
Aim i) Identify and physiologically validate novel Golgi-resident substrates of meprin β and assess their processing by cancer-associated meprin β variants and in the context of colorectal cancer models
Aim ii)Illuminate the trafficking and the molecular mechanisms enabling activation of meprin β within the early secretory pathway
Regulation of proteolytic activity of meprin β. Meprin β is guided through the secretory pathway and can reach the cell surface as an inactive zymogen. As preliminary data suggests meprin β activity already in the secretory pathway, we aim to (I) Identify Golgi-resident substrates of meprin β and cancer-associated meprin β variants and (II) in detail illuminate trafficking and activation of meprin β within the secretory pathway
