FRMD8 promotes inflammatory and growth factor signalling by stabilising the iRhom/ADAM17 sheddase complex

• DOI: 10.7554/elife.35012
• Publication Date: 2018-06-15T14:23:30Z
• Authors: Ulrike Künzel; Adam Graham Grieve; Yao Meng; Boris Sieber; Sally A Cowley; Matthew Freeman
• Keywords: Signalling

Many intercellular signals are synthesised as transmembrane precursors that released by proteolytic cleavage ('shedding') from the cell surface. ADAM17, a membrane-tethered metalloprotease, is primary shedding enzyme responsible for release of inflammatory cytokine TNFα and several EGF receptor ligands. ADAM17 exists in complex with rhomboid-like iRhom proteins, which act cofactors regulate substrate shedding. Here we report poorly characterised FERM domain-containing protein FRMD8 new component iRhom2/ADAM17 sheddase complex. binds to cytoplasmic N-terminus iRhoms necessary stabilise at In absence FRMD8, iRhom2 degraded via endolysosomal pathway, resulting reduction ADAM17-mediated We have confirmed pathophysiological significance iPSC-derived human macrophages mouse tissues, thus demonstrating its role regulated multiple growth factor signals.