Journal article

A toolbox for imaging RIPK1, RIPK3, and MLKL in mouse and human cells

Andre L Samson, Cheree Fitzgibbon, Komal M Patel, Joanne M Hildebrand, Lachlan W Whitehead, Joel S Rimes, Annette V Jacobsen, Christopher R Horne, Xavier J Gavin, Samuel N Young, Kelly L Rogers, Edwin D Hawkins, James M Murphy



Necroptosis is a lytic, inflammatory cell death pathway that is dysregulated in many human pathologies. The pathway is executed by a core machinery comprising the RIPK1 and RIPK3 kinases, which assemble into necrosomes in the cytoplasm, and the terminal effector pseudokinase, MLKL. RIPK3-mediated phosphorylation of MLKL induces oligomerization and translocation to the plasma membrane where MLKL accumulates as hotspots and perturbs the lipid bilayer to cause death. The precise choreography of events in the pathway, where they occur within cells, and pathway differences between species, are of immense interest. However, they have been poorly characterized due to a dearth of validated antibodie..

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Awarded by Australian National Health and Medical Research Council

Funding Acknowledgements

We are grateful to the Australian National Health and Medical Research Council for fellowship (JMH, 1142669; EDH, 1159488; JMM, 1172929), grant (1124735, 1124737, 1105023 and 2002965), and infrastructure (IRIISS 9000653) support, with additional support from the CASS Foundation (ALS) and the Victorian Government Operational Infrastructure Support scheme. We acknowledge the support for AVJ from an Australian Research Training Program Scholarship.