A motif within the armadillo repeat of Parkinson's-linked LRRK2 interacts with FADD to hijack the extrinsic death pathway

Scientific Reports

Volumn 8, Issue 1, 2018, Pages

  Antoniou, Nasia ^a   Vlachakis, Dimitrios ^a   Memou, Anna ^a   Leandrou, Emmanouela ^a   Valkimadi, Polytimi Eleni ^a   Melachroinou, Katerina ^a   Re, Diane B ^b   Przedborski, Serge ^b   Dauer, William T ^c   Stefanis, Leonidas ^a,d   Rideout, Hardy J ^a  

^a BIOMEDICAL RESEARCH FOUNDATION   (Greece)

^b Columbia University ^*  (United States)

^c UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^d UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

Author keywords

[No Author keywords available]

Indexed keywords

ARMADILLO DOMAIN PROTEIN; BAX PROTEIN, HUMAN; BID PROTEIN, HUMAN; FADD PROTEIN, HUMAN; FAS ASSOCIATED DEATH DOMAIN PROTEIN; LEUCINE RICH REPEAT KINASE 2; LRRK2 PROTEIN, HUMAN; PROTEIN BAX; PROTEIN BID;

AMINO ACID REPEAT; ANIMAL; CELL DEATH; CYTOLOGY; GENETICS; HEK293 CELL LINE; HUMAN; METABOLISM; MOLECULAR DOCKING; MOUSE; NERVE CELL; PARKINSON DISEASE; PRIMARY CELL CULTURE; PROTEIN ANALYSIS; PROTEIN DOMAIN; RAT; SIGNAL TRANSDUCTION;

ANIMALS; ARMADILLO DOMAIN PROTEINS; BCL-2-ASSOCIATED X PROTEIN; BH3 INTERACTING DOMAIN DEATH AGONIST PROTEIN; CELL DEATH; FAS-ASSOCIATED DEATH DOMAIN PROTEIN; HEK293 CELLS; HUMANS; LEUCINE-RICH REPEAT SERINE-THREONINE PROTEIN KINASE-2; MICE; MOLECULAR DOCKING SIMULATION; NEURONS; PARKINSON DISEASE; PRIMARY CELL CULTURE; PROTEIN INTERACTION DOMAINS AND MOTIFS; PROTEIN INTERACTION MAPPING; RATS; REPETITIVE SEQUENCES, AMINO ACID; SIGNAL TRANSDUCTION;

EID: 85042542741     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/s41598-018-21931-8     Document Type: Article

References (45)

1. Ho, C. C., Rideout, H. J., Ribe, E., Troy, C. M. & Dauer, W. T. The Parkinson disease protein leucine-rich repeat kinase 2 transduces death signals via Fas-associated protein with death domain and caspase-8 in a cellular model of neurodegeneration. J Neurosci 29, 1011-1016, https://doi.org/10.1523/JNEUROSCI.5175-08.2009 (2009).
2. Skibinski, G., Nakamura, K., Cookson, M. R. & Finkbeiner, S. Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and synuclein but not kinase activity or inclusion bodies. J Neurosci 34, 418-433, https://doi.org/10.1523/JNEUROSCI.2712-13.2014 (2014).
3. Smith, W. W. et al. Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. Proc Natl Acad Sci USA 102, 18676-18681, https://doi.org/10.1073/pnas.0508052102 (2005).
4. West, A. B. et al. Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. Hum Mol Genet 16, 223-232, https://doi.org/10.1093/hmg/ddl471 (2007).
5. Greggio, E. et al. Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. Neurobiology of disease 23, 329-341 (2006).
6. Kett, L. R. et al. LRRK2 Parkinson disease mutations enhance its microtubule association. Hum Mol Genet 21, 890-899, https://doi.org/10.1093/hmg/ddr526 (2012).
7. Melachroinou, K. et al. Activation of FADD-Dependent Neuronal Death Pathways as a Predictor of Pathogenicity for LRRK2 Mutations. PLoS One 11, e0166053, https://doi.org/10.1371/journal.pone.0166053 (2016).
8. Chen, C. Y. et al. (G2019S) LRRK2 activates MKK4-JNK pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD. Cell Death Differ 19, 1623-1633, https://doi.org/10.1038/cdd.2012.42 (2012).
9. Iaccarino, C. et al. Apoptotic mechanisms in mutant LRRK2-mediated cell death. Hum Mol Genet 16, 1319-1326, https://doi.org/10.1093/hmg/ddm080 (2007).
10. Guicciardi, M. E. & Gores, G. J. Life and death by death receptors. FASEB journal: official publication of the Federation of American Societies for Experimental Biology 23, 1625-1637, https://doi.org/10.1096/fj.08-111005 (2009).
11. Vila, M. et al. Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. Proc Natl Acad Sci USA 98, 2837-2842, https://doi.org/10.1073/pnas.051633998 (2001).
12. Wang, D. B. et al. Bax interacting factor-1 promotes survival and mitochondrial elongation in neurons. J Neurosci 34, 2674-2683, https://doi.org/10.1523/JNEUROSCI.4074-13.2014 (2014).
13. Jantas, D. & Lason, W. Protective effect of memantine against Doxorubicin toxicity in primary neuronal cell cultures: influence a development stage. Neurotoxicity research 15, 24-37, https://doi.org/10.1007/s12640-009-9002-8 (2009).
14. Wetzel, M., Tibbitts, J., Rosenberg, G. A. & Cunningham, L. A. Vulnerability of mouse cortical neurons to doxorubicin-induced apoptosis is strain-dependent and is correlated with mRNAs encoding Fas, Fas-Ligand, and metalloproteinases. Apoptosis: an international journal on programmed cell death 9, 649-656, https://doi.org/10.1023/B:APPT.0000038038.42809.e2 (2004).
15. Nagai, M. et al. Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nature neuroscience 10, 615-622, https://doi.org/10.1038/nn1876 (2007).
16. Becattini, B. et al. Targeting apoptosis via chemical design: inhibition of bid-induced cell death by small organic molecules. Chem Biol 11, 1107-1117, https://doi.org/10.1016/j.chembiol.2004.05.022 S1074552104001917 [pii] (2004).
17. Civiero, L. et al. Biochemical characterization of highly purified leucine-rich repeat kinases 1 and 2 demonstrates formation of homodimers. PLoS One 7, e43472 (2012).
18. Greggio, E. et al. The Parkinson disease-associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intramolecular autophosphorylation. J Biol Chem 283, 16906-16914 (2008).
19. Miyatake, H. et al. Crystal structure of human importin-alpha1 (Rch1), revealing a potential autoinhibition mode involving homodimerization. PLoS One 10, e0115995, https://doi.org/10.1371/journal.pone.0115995 (2015).
20. Cardona, F., Tormos-Perez, M. & Perez-Tur, J. Structural and functional in silico analysis of LRRK2 missense substitutions. Molecular biology reports 41, 2529-2542, https://doi.org/10.1007/s11033-014-3111-z (2014).
21. Guaitoli, G. et al. Structural model of the dimeric Parkinson's protein LRRK2 reveals a compact architecture involving distant interdomain contacts. Proc Natl Acad Sci USA 113, E4357-4366, https://doi.org/10.1073/pnas.1523708113 (2016).
22. Lu, B. et al. Expression, purification and preliminary biochemical studies of the N-terminal domain of leucine-rich repeat kinase 2. Biochim Biophys Acta 1804, 1780-1784, https://doi.org/10.1016/j.bbapap.2010.05.004 (2010).
23. Sandu, C. et al. FADD self-association is required for stable interaction with an activated death receptor. Cell Death Differ 13, 2052-2061, https://doi.org/10.1038/sj.cdd.4401966 (2006).
24. Xiromerisiou, G. et al. Screening for SNCA and LRRK2 mutations in Greek sporadic and autosomal dominant Parkinson's disease: identification of two novel LRRK2 variants. European journal of neurology: the official journal of the European Federation of Neurological Societies 14, 7-11, https://doi.org/10.1111/j.1468-1331.2006.01551.x (2007).
25. Riley, J. S., Malik, A., Holohan, C. & Longley, D. B. DED or alive: assembly and regulation of the death effector domain complexes. Cell death & disease 6, e1866, https://doi.org/10.1038/cddis.2015.213 (2015).
26. Carrington, P. E. et al. The structure of FADD and its mode of interaction with procaspase-8. Molecular cell 22, 599-610, https://doi.org/10.1016/j.molcel.2006.04.018 (2006).
27. Eberstadt, M. et al. NMR structure and mutagenesis of the FADD (Mort1) death-effector domain. Nature 392, 941-945, https://doi.org/10.1038/31972 (1998).
28. Kaufmann, M. et al. Identification of a basic surface area of the FADD death effector domain critical for apoptotic signaling. FEBS letters 527, 250-254 (2002).
29. Kodiha, M., Tran, D., Morogan, A., Qian, C. & Stochaj, U. Dissecting the signaling events that impact classical nuclear import and target nuclear transport factors. PLoS One 4, e8420, https://doi.org/10.1371/journal.pone.0008420 (2009).
30. Liu, Z. et al. The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease. Nature immunology 12, 1063-1070, https://doi.org/10.1038/ni.2113 (2011).
31. Park, S. et al. Interplay between Leucine-Rich Repeat Kinase 2 (LRRK2) and p62/SQSTM-1 in Selective Autophagy. PLoS One 11, e0163029, https://doi.org/10.1371/journal.pone.0163029 (2016).
32. Gomez-Angelats, M. & Cidlowski, J. A. Molecular evidence for the nuclear localization of FADD. Cell Death Differ 10, 791-797, https://doi.org/10.1038/sj.cdd.4401237 (2003).
33. Smith, W. W. et al. Kinase activity of mutant LRRK2 mediates neuronal toxicity. Nature neuroscience 9, 1231-1233, https://doi.org/10.1038/nn1776 (2006).
34. Herzig, M. C. et al. LRRK2 protein levels are determined by kinase function and are crucial for kidney and lung homeostasis in mice. Hum Mol Genet 20, 4209-4223, https://doi.org/10.1093/hmg/ddr348 (2011).
35. Steger, M. et al. Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases. eLife 5, https://doi.org/10.7554/eLife.12813 (2016).
36. Kantari, C. & Walczak, H. Caspase-8 and bid: caught in the act between death receptors and mitochondria. Biochim Biophys Acta 1813, 558-563, https://doi.org/10.1016/j.bbamcr.2011.01.026 (2011).
37. Raemy, E. & Martinou, J. C. Involvement of cardiolipin in tBID-induced activation of BAX during apoptosis. Chemistry and physics of lipids 179, 70-74, https://doi.org/10.1016/j.chemphyslip.2013.12.002 (2014).
38. Ho, D. H. et al. Leucine-Rich Repeat Kinase 2 (LRRK2) phosphorylates p53 and induces p21(WAF1/CIP1) expression. Molecular brain 8, 54, https://doi.org/10.1186/s13041-015-0145-7 (2015).
39. Cui, J., Yu, M., Niu, J., Yue, Z. & Xu, Z. Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits the processing of uMtCK to induce cell death in a cell culture model system. Bioscience reports 31, 429-437, https://doi.org/10.1042/BSR20100127 (2011).
40. Greggio, E. et al. Mutations in LRRK2/dardarin associated with Parkinson disease are more toxic than equivalent mutations in the homologous kinase LRRK1. Journal of neurochemistry 102, 93-102 (2007).
41. Gahl, R. F., Dwivedi, P. & Tjandra, N. Bcl-2 proteins bid and bax form a network to permeabilize the mitochondria at the onset of apoptosis. Cell death & disease 7, e2424, https://doi.org/10.1038/cddis.2016.320 (2016).
42. Rideout, H. J. & Stefanis, L. Proteasomal inhibition-induced inclusion formation and death in cortical neurons require transcription and ubiquitination. Molecular and cellular neurosciences 21, 223-238 (2002).
43. Perez, D. & White, E. E1B 19K inhibits Fas-mediated apoptosis through FADD-dependent sequestration of FLICE. The Journal of cell biology 141, 1255-1266 (1998).
44. Siegel, R. M. et al. Death-effector filaments: novel cytoplasmic structures that recruit caspases and trigger apoptosis. The Journal of cell biology 141, 1243-1253 (1998).
45. Scott, F. L. et al. The Fas-FADD death domain complex structure unravels signalling by receptor clustering. Nature 457, 1019-1022, https://doi.org/10.1038/nature07606 (2009).