Spatio-temporal regulation of the iRhom-ADAM17 complex

Overall, a detailed picture of the life cycle of the iRhom-ADAM17 complex is still missing. We were already able to identify iCERES (Project B) as a crucial element for Golgi entry. However, the exact progression and kinetics of the iRhom-ADAM17 complex with respect to transport through the secretory pathway, stability at the cell surface and internalisation with recycling or lysosomal degradation remain unclear [1]. We are therefore investigating the subcellular localisation as well as the kinetics of the iRhom-ADAM17 complex using cell biological approaches such as (confocal) fluorescence microscopy and biochemical experiments such as pulse-chase experiments. In our first interactome study (Project C) of iRhom2, we found several proteins involved in intracellular vesicle trafficking [2], which we will analyse in further detail.

References

[1] Lorenzen, I., … and S. Düsterhöft (2016). "Control of ADAM17 activity by regulation of its cellular localisation." Sci Rep 6: 35067. DOI: 10.1038/srep35067

[2] Düsterhöft, S., et al. (2021). "The iRhom homology domain is indispensable for ADAM17-mediated TNFalpha and EGF receptor ligand release." Cell Mol Life Sci 78(11):5015-5040. DOI: 10.1007/s00018-021-03845-3