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MLKL Compromises Plasma Membrane Integrity by Binding to Phosphatidylinositol Phosphates
Open accessAbstract
Although mixed lineage kinase domain-like (MLKL) protein has emerged as a specific and crucial protein for necroptosis induction, how MLKL transduces the death signal remains poorly understood. Here, we demonstrate that the full four-helical bundle domain (4HBD) in the N-terminal region of MLKL is required and sufficient to induce its oligomerization and trigger cell death. Moreover, we found that a patch of positively charged amino acids on the surface of the 4HBD binds to phosphatidylinositol phosphates (PIPs) and allows recruitment of MLKL to the plasma membrane. Importantly, we found that recombinant MLKL, but not a mutant lacking these positive charges, induces leakage of PIP-containing liposomes as potently as BAX, supporting a model in which MLKL induces necroptosis by directly permeabilizing the plasma membrane. Accordingly, we found that inhibiting the formation of PI(5)P and PI(4,5)P2 specifically inhibits tumor necrosis factor (TNF)-mediated necroptosis but not apoptosis.
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Cites
Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy
Czabotar, P. E., Lessene, G., Strasser, A., & Adams, J. M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3722 · Cited by 3,219
Cho, Y., Challa, S., Moquin, D., Genga, R., Ray, T. D., Guildford, M., & Chan, F. K.-M. (2009) · Cell · doi:10.1016/j.cell.2009.05.037 · Cited by 2,435
Receptor Interacting Protein Kinase-3 Determines Cellular Necrotic Response to TNF-α
He, S., Wang, L., Miao, L., Wang, T., Du, F., Zhao, L., & Wang, X. (2009) · Cell · doi:10.1016/j.cell.2009.05.021 · Cited by 2,214
RIP3, an Energy Metabolism Regulator That Switches TNF-Induced Cell Death from Apoptosis to Necrosis
Zhang, D.-W., Shao, J., Lin, J., Zhang, N., Lu, B.-J., Lin, S.-C., Dong, M.-Q., & Han, J. (2009) · Science · doi:10.1126/science.1172308 · Cited by 1,931
Regulated necrosis: the expanding network of non-apoptotic cell death pathways
Berghe, T. V., Linkermann, A., Jouan-Lanhouet, S., Walczak, H., & Vandenabeele, P. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3737 · Cited by 1,735
Self-citationPlasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis
Cai, Z., Jitkaew, S., Zhao, J., Chiang, H.-C., Choksi, S., Liu, J., Ward, Y., Wu, L.-G., & Liu, Z.-G. (2014) · Nature Cell Biology · doi:10.1038/ncb2883 · Cited by 1,322
Li, J., McQuade, T., Siemer, A. B., Napetschnig, J., Moriwaki, K., Hsiao, Y.-S., Damko, E., Moquin, D., Walz, T., McDermott, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.019 · Cited by 1,222
The Pseudokinase MLKL Mediates Necroptosis via a Molecular Switch Mechanism
Murphy, J. M., Czabotar, P. E., Hildebrand, J. M., Lucet, I. S., Zhang, J.-G., Alvarez-Diaz, S., Lewis, R., Lalaoui, N., Metcalf, D., Webb, A. I., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.06.018 · Cited by 1,220
PIP 2 Is a Necessary Cofactor for Ion Channel Function: How and Why?
Suh, B.-C., & Hille, B. (2008) · Annual Review of Biophysics · doi:10.1146/annurev.biophys.37.032807.125859 · Cited by 646
Receptor Activation Alters Inner Surface Potential During Phagocytosis
Yeung, T., Terebiznik, M., Yu, L., Silvius, J., Abidi, W. M., Philips, M., Levine, T., Kapus, A., & Grinstein, S. (2006) · Science · doi:10.1126/science.1129551 · Cited by 329
Research works printed but not linked: 25
- Antonsson, 1997, Inhibition of Bax channel-forming activity by Bcl-2, Science, 277, 370, 10.1126/science.277.5324.370 · DOI · Paper page
- Biton, 2011, NEMO and RIP1 control cell fate in response to extensive DNA damage via TNF-α feedforward signaling, Cell, 145, 92, 10.1016/j.cell.2011.02.023 · DOI · Paper page
- Chen, 2013, Diverse sequence determinants control human and mouse receptor interacting protein 3 (RIP3) and mixed lineage kinase domain-like (MLKL) interaction in necroptotic signaling, J. Biol. Chem., 288, 16247, 10.1074/jbc.M112.435545 · DOI · Paper page
- Chen, 2014, Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death, Cell Res., 24, 105, 10.1038/cr.2013.171 · DOI · Paper page
- Cho, 2005, Membrane-protein interactions in cell signaling and membrane trafficking, Annu. Rev. Biophys. Biomol. Struct., 34, 119, 10.1146/annurev.biophys.33.110502.133337 · DOI · Paper page
- Dondelinger, 2013, RIPK3 contributes to TNFR1-mediated RIPK1 kinase-dependent apoptosis in conditions of cIAP1/2 depletion or TAK1 kinase inhibition, Cell Death Differ., 20, 1381, 10.1038/cdd.2013.94 · DOI · Paper page
- Duprez, 2011, RIP kinase-dependent necrosis drives lethal systemic inflammatory response syndrome, Immunity, 35, 908, 10.1016/j.immuni.2011.09.020 · DOI · Paper page
- Garcia, 1995, The pleckstrin homology domain of phospholipase C-delta 1 binds with high affinity to phosphatidylinositol 4,5-bisphosphate in bilayer membranes, Biochemistry, 34, 16228, 10.1021/bi00049a039 · DOI · Paper page
- Kaczmarek, 2013, Necroptosis: the release of damage-associated molecular patterns and its physiological relevance, Immunity, 38, 209, 10.1016/j.immuni.2013.02.003 · DOI · Paper page
- Linkermann, 2013, Two independent pathways of regulated necrosis mediate ischemia-reperfusion injury, Proc. Natl. Acad. Sci. USA, 110, 12024, 10.1073/pnas.1305538110 · DOI · Paper page
- Mocarski, 2012, Viral infection and the evolution of caspase 8-regulated apoptotic and necrotic death pathways, Nat. Rev. Immunol., 12, 79, 10.1038/nri3131 · DOI · Paper page
- Parker, 2005, Pore-forming protein toxins: from structure to function, Prog. Biophys. Mol. Biol., 88, 91, 10.1016/j.pbiomolbio.2004.01.009 · DOI · Paper page
- Rameh, 1997, A comparative analysis of the phosphoinositide binding specificity of pleckstrin homology domains, J. Biol. Chem., 272, 22059, 10.1074/jbc.272.35.22059 · DOI · Paper page
- Remijsen, 2014, Depletion of RIPK3 or MLKL blocks TNF-driven necroptosis and switches towards a delayed RIPK1 kinase-dependent apoptosis, Cell Death Dis., 5, e1004, 10.1038/cddis.2013.531 · DOI
- Salim, 1996, Distinct specificity in the recognition of phosphoinositides by the pleckstrin homology domains of dynamin and Bruton’s tyrosine kinase, EMBO J., 15, 6241, 10.1002/j.1460-2075.1996.tb01014.x · DOI · Paper page
- Sun, 2012, Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase, Cell, 148, 213, 10.1016/j.cell.2011.11.031 · DOI · Paper page
- Vanden Berghe, 2010, Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features, Cell Death Differ., 17, 922, 10.1038/cdd.2009.184 · DOI · Paper page
- Vanlangenakker, 2008, Molecular mechanisms and pathophysiology of necrotic cell death, Curr. Mol. Med., 8, 207, 10.2174/156652408784221306 · DOI · Paper page
- Vanlangenakker, 2011, TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members, Cell Death Dis., 2, e230, 10.1038/cddis.2011.111 · DOI
- Wang, 2008, TNF-alpha induces two distinct caspase-8 activation pathways, Cell, 133, 693, 10.1016/j.cell.2008.03.036 · DOI · Paper page
- Wang, 2012, The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways, Cell, 148, 228, 10.1016/j.cell.2011.11.030 · DOI · Paper page
- Wang, 2014, Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3, Mol. Cell, 54, 133, 10.1016/j.molcel.2014.03.003 · DOI · Paper page
- Wu, 2013, Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis, Cell Res., 23, 994, 10.1038/cr.2013.91 · DOI · Paper page
- Xie, 2013, Structural insights into RIP3-mediated necroptotic signaling, Cell Rep, 5, 70, 10.1016/j.celrep.2013.08.044 · DOI
- Zhao, 2012, Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis, Proc. Natl. Acad. Sci. USA, 109, 5322, 10.1073/pnas.1200012109 · DOI · Paper page
Cited by
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
Self-citationInflammasome-activated gasdermin D causes pyroptosis by forming membrane pores
Liu, X., Zhang, Z., Ruan, J., Pan, Y., Magupalli, V. G., Wu, H., & Lieberman, J. (2016) · Nature · doi:10.1038/nature18629 · Cited by 3,202
Immunogenic cell death in cancer and infectious disease
Galluzzi, L., Buqué, A., Kepp, O., Zitvogel, L., & Kroemer, G. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2016.107 · Cited by 3,119
Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death
Shi, J., Gao, W., & Shao, F. (2017) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.10.004 · Cited by 3,088
Pore-forming activity and structural autoinhibition of the gasdermin family
Ding, J., Wang, K., Liu, W., She, Y., Sun, Q., Shi, J., Sun, H., Wang, D.-C., & Shao, F. (2016) · Nature · doi:10.1038/nature18590 · Cited by 2,771
Metadata
- Authors
- Dondelinger, Y., Declercq, W., Montessuit, S., Roelandt, R., Goncalves, A., Bruggeman, I., Hulpiau, P., Weber, K., Sehon, C. A., Marquis, R. W., Bertin, J., Gough, P. J., Savvides, S., Martinou, J.-C., Bertrand, M. J. M., & Vandenabeele, P.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 7
- Issue
- 4
- Pages
- 971-981
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2077317536
- Cited by
- 815
- References
- 11
- FWCI
- 24.82
- Type
- journal article
- Language
- en
- Open access
- gold
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- creativecommons.org/licenses/by-nc-nd/3.0/ (vor)
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- Dondelinger, Y., Declercq, W., Montessuit, S., Roelandt, R., Goncalves, A., Bruggeman, I., Hulpiau, P., Weber, K., Sehon, C. A., Marquis, R. W., Bertin, J., Gough, P. J., Savvides, S., Martinou, J.-C., Bertrand, M. J. M., & Vandenabeele, P. (2014). MLKL Compromises Plasma Membrane Integrity by Binding to Phosphatidylinositol Phosphates. Cell Reports. https://doi.org/10.1016/j.celrep.2014.04.026
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