Dataset: Proteomics of ADAM17 and iRhom2 KO microglia using high-performance secretome protein enrichment with click sugars

The cell surface receptor TREM2 is a key genetic risk factor and drug target in Alzheimer’s disease (AD). In the brain, TREM2 is expressed in microglia, where it undergoes proteolytic cleavage, linked to AD risk, but the responsible protease in microglia is unknown. Another microglia-expressed AD risk factor is inactive rhomboid 2 (iRhom2, RHBDF2), which acts as a non-catalytic subunit of the metalloprotease ADAM17. Its function in AD is unknown. To determine whether loss of iRhom2 and ADAM17 leads to a reduction of cleavage of additional membrane proteins beyond TNF, we used the ‘high-performance secretome protein enrichment with click sugars’ (hiSPECS) method for mass spectrometry-based secretome analysis (Tüshaus et al, 2020). hiSPECS uses a metabolic labeling with click sugars, which allows to culture cells in the presence of serum or serum-like supplements. Therefore, we have used the murine microglia of wild-type and RHBDF2/iRhom2 KO mice.