Mutant prion proteins increase calcium permeability of AMPA receptors, exacerbating excitotoxicity
Autoři:
Elsa Ghirardini aff001; Elena Restelli aff002; Raffaella Morini aff001; Ilaria Bertani aff002; Davide Ortolan aff002; Fabio Perrucci aff001; Davide Pozzi aff001; Michela Matteoli aff001; Roberto Chiesa aff002
Působiště autorů:
Laboratory of Pharmacology and Brain Pathology, Humanitas Clinical and Research Center, Rozzano—Milan, Italy
aff001; Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
aff002; Consiglio Nazionale delle Ricerche Institute of Neuroscience, Milan, Italy
aff003
Vyšlo v časopise:
Mutant prion proteins increase calcium permeability of AMPA receptors, exacerbating excitotoxicity. PLoS Pathog 16(7): e1008654. doi:10.1371/journal.ppat.1008654
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.ppat.1008654
Souhrn
Prion protein (PrP) mutations are linked to genetic prion diseases, a class of phenotypically heterogeneous neurodegenerative disorders with invariably fatal outcome. How mutant PrP triggers neurodegeneration is not known. Synaptic dysfunction precedes neuronal loss but it is not clear whether, and through which mechanisms, disruption of synaptic activity ultimately leads to neuronal death. Here we show that mutant PrP impairs the secretory trafficking of AMPA receptors (AMPARs). Specifically, intracellular retention of the GluA2 subunit results in synaptic exposure of GluA2-lacking, calcium-permeable AMPARs, leading to increased calcium permeability and enhanced sensitivity to excitotoxic cell death. Mutant PrPs linked to different genetic prion diseases affect AMPAR trafficking and function in different ways. Our findings identify AMPARs as pathogenic targets in genetic prion diseases, and support the involvement of excitotoxicity in neurodegeneration. They also suggest a mechanistic explanation for how different mutant PrPs may cause distinct disease phenotypes.
Klíčová slova:
Cell membranes – Genetics of disease – HeLa cells – Neuronal death – Neuronal dendrites – Neurons – Prion diseases – Fatal familial insomnia
Zdroje
1. Kim M-O, Takada LT, Wong K, Forner SA, Geschwind MD. Genetic PrP prion diseases. Cold Spring Harb Perspect Biol. 2018;10. doi: 10.1101/cshperspect.a033134 28778873
2. Monari L, Chen SG, Brown P, Parchi P, Petersen RB, Mikol J, et al. Fatal familial insomnia and familial Creutzfeldt-Jakob disease: different prion proteins determined by a DNA polymorphism. Proc Natl Acad Sci U S A. 1994;91: 2839–42. doi: 10.1073/pnas.91.7.2839 7908444
3. Senatore A, Restelli E, Chiesa R. Synaptic dysfunction in prion diseases: a trafficking problem? Int J Cell Biol. 2013;2013: 543803. doi: 10.1155/2013/543803 24369467
4. Steinert JR. Prion protein as a mediator of synaptic transmission. Commun Integr Biol. 2015;8: e1063753. doi: 10.1080/19420889.2015.1063753 26478992
5. Senatore A, Colleoni S, Verderio C, Restelli E, Morini R, Condliffe SB, et al. Mutant PrP suppresses glutamatergic neurotransmission in cerebellar granule neurons by impairing membrane delivery of VGCC alpha(2)delta-1 subunit. Neuron. 2012;74: 300–13. doi: 10.1016/j.neuron.2012.02.027 22542184
6. Kleene R, Loers G, Langer J, Frobert Y, Buck F, Schachner M. Prion protein regulates glutamate-dependent lactate transport of astrocytes. J Neurosci. 2007;27: 12331–40. doi: 10.1523/JNEUROSCI.1358-07.2007 17989297
7. Watt NT, Taylor DR, Kerrigan TL, Griffiths HH, Rushworth JV, Whitehouse IJ, et al. Prion protein facilitates uptake of zinc into neuronal cells. Nat Commun. 2012;3: 1134. doi: 10.1038/ncomms2135 23072804
8. Greger IH, Khatri L, Kong X, Ziff EB. AMPA receptor tetramerization is mediated by Q/R editing. Neuron. 2003;40: 763–774. doi: 10.1016/s0896-6273(03)00668-8 14622580
9. Swanson GT, Kamboj SK, Cull-Candy SG. Single-channel properties of recombinant AMPA receptors depend on RNA editing, splice variation, and subunit composition. J Neurosci. 1997;17: 58–69. doi: 10.1523/JNEUROSCI.17-01-00058.1997 8987736
10. Chater TE, Goda Y. The role of AMPA receptors in postsynaptic mechanisms of synaptic plasticity. Front Cell Neurosci. 2014;8: 401. doi: 10.3389/fncel.2014.00401 25505875
11. Bouybayoune I, Mantovani S, Del Gallo F, Bertani I, Restelli E, Comerio L, et al. Transgenic fatal familial insomnia mice indicate prion infectivity-independent mechanisms of pathogenesis and phenotypic expression of disease. PLoS Pathog. 2015;11: e1004796. doi: 10.1371/journal.ppat.1004796 25880443
12. Chiesa R, Piccardo P, Ghetti B, Harris DA. Neurological illness in transgenic mice expressing a prion protein with an insertional mutation. Neuron. 1998;21: 1339–51. doi: 10.1016/s0896-6273(00)80653-4 [pii] 9883727
13. Chiesa R, Drisaldi B, Quaglio E, Migheli A, Piccardo P, Ghetti B, et al. Accumulation of protease-resistant prion protein (PrP) and apoptosis of cerebellar granule cells in transgenic mice expressing a PrP insertional mutation. Proc Natl Acad Sci U S A. 2000;97: 5574–9. doi: 10.1073/pnas.97.10.5574 [pii] 10805813
14. Dossena S, Imeri L, Mangieri M, Garofoli A, Ferrari L, Senatore A, et al. Mutant prion protein expression causes motor and memory deficits and abnormal sleep patterns in a transgenic mouse model. Neuron. 2008;60: 598–609. doi: 10.1016/j.neuron.2008.09.008 19038218
15. Campeau JL, Wu G, Bell JR, Rasmussen J, Sim VL. Early increase and late decrease of purkinje cell dendritic spine density in prion-infected organotypic mouse cerebellar cultures. PLoS ONE. 2013;8: e81776. doi: 10.1371/journal.pone.0081776 24312586
16. Fang C, Imberdis T, Garza MC, Wille H, Harris DA. A neuronal culture system to detect prion synaptotoxicity. PLoS Pathog. 2016;12: e1005623. doi: 10.1371/journal.ppat.1005623 27227882
17. Fang C, Wu B, Le NTT, Imberdis T, Mercer RCC, Harris DA. Prions activate a p38 MAPK synaptotoxic signaling pathway. PLoS Pathog. 2018;14: e1007283. doi: 10.1371/journal.ppat.1007283 30235355
18. Fuhrmann M, Mitteregger G, Kretzschmar H, Herms J. Dendritic pathology in prion disease starts at the synaptic spine. J Neurosci. 2007;27: 6224–6233. doi: 10.1523/JNEUROSCI.5062-06.2007 17553995
19. Drisaldi B, Stewart RS, Adles C, Stewart LR, Quaglio E, Biasini E, et al. Mutant PrP is delayed in its exit from the endoplasmic reticulum, but neither wild-type nor mutant PrP undergoes retrotranslocation prior to proteasomal degradation. J Biol Chem. 2003;278: 21732–43. doi: 10.1074/jbc.M213247200 12663673
20. Ivanova L, Barmada S, Kummer T, Harris DA. Mutant prion proteins are partially retained in the endoplasmic reticulum. J Biol Chem. 2001;276: 42409–21. doi: 10.1074/jbc.M106928200 11527974
21. Massignan T, Biasini E, Lauranzano E, Veglianese P, Pignataro M, Fioriti L, et al. Mutant prion protein expression is associated with an alteration of the Rab GDP dissociation inhibitor alpha (GDI)/Rab11 pathway. Mol Cell Proteomics. 2010;9: 611–22. doi: 10.1074/mcp.M900271-MCP200 19996123
22. Fioriti L, Dossena S, Stewart LR, Stewart RS, Harris DA, Forloni G, et al. Cytosolic prion protein (PrP) is not toxic in N2a cells and primary neurons expressing pathogenic PrP mutations. J Biol Chem. 2005;280: 11320–8. doi: 10.1074/jbc.M412441200 15632159
23. Gorodinsky A, Harris DA. Glycolipid-anchored proteins in neuroblastoma cells form detergent-resistant complexes without caveolin. J Cell Biol. 1995;129: 619–27. doi: 10.1083/jcb.129.3.619 7537273
24. Vey M, Pilkuhn S, Wille H, Nixon R, DeArmond SJ, Smart EJ, et al. Subcellular colocalization of the cellular and scrapie prion proteins in caveolae-like membranous domains. Proc Natl Acad Sci USA. 1996;93: 14945–14949. doi: 10.1073/pnas.93.25.14945 8962161
25. Hering H, Lin C-C, Sheng M. Lipid rafts in the maintenance of synapses, dendritic spines, and surface AMPA receptor stability. J Neurosci. 2003;23: 3262–3271. doi: 10.1523/JNEUROSCI.23-08-03262.2003 12716933
26. Hou Q, Huang Y, Amato S, Snyder SH, Huganir RL, Man H-Y. Regulation of AMPA receptor localization in lipid rafts. Molecular and Cellular Neuroscience. 2008;38: 213–223. doi: 10.1016/j.mcn.2008.02.010 18411055
27. Cole AA, Dosemeci A, Reese TS. Co-segregation of AMPA receptors with G(M1) ganglioside in synaptosomal membrane subfractions. Biochem J. 2010;427: 535–540. doi: 10.1042/BJ20091344 20148761
28. Turrigiano GG, Leslie KR, Desai NS, Rutherford LC, Nelson SB. Activity-dependent scaling of quantal amplitude in neocortical neurons. Nature. 1998;391: 892–896. doi: 10.1038/36103 9495341
29. Gainey MA, Hurvitz-Wolff JR, Lambo ME, Turrigiano GG. Synaptic scaling requires the GluR2 subunit of the AMPA receptor. J Neurosci. 2009;29: 6479–89. doi: 10.1523/JNEUROSCI.3753-08.2009 19458219
30. Wierenga CJ, Ibata K, Turrigiano GG. Postsynaptic expression of homeostatic plasticity at neocortical synapses. J Neurosci. 2005;25: 2895–2905. doi: 10.1523/JNEUROSCI.5217-04.2005 15772349
31. Washburn MS, Numberger M, Zhang S, Dingledine R. Differential dependence on GluR2 expression of three characteristic features of AMPA receptors. J Neurosci. 1997;17: 9393–9406. doi: 10.1523/JNEUROSCI.17-24-09393.1997 9390995
32. Garbelli R, Inverardi F, Medici V, Amadeo A, Verderio C, Matteoli M, et al. Heterogeneous expression of SNAP-25 in rat and human brain. J Comp Neurol. 2008;506: 373–386. doi: 10.1002/cne.21505 18041776
33. Borchelt DR, Davis J, Fischer M, Lee MK, Slunt HH, Ratovitsky T, et al. A vector for expressing foreign genes in the brains and hearts of transgenic mice. Genet Anal. 1996;13: 159–63. doi: 10.1016/s1050-3862(96)00167-2 9117892
34. Larm JA, Cheung NS, Beart PM. Apoptosis induced via AMPA-selective glutamate receptors in cultured murine cortical neurons. J Neurochem. 1997;69: 617–622. doi: 10.1046/j.1471-4159.1997.69020617.x 9231719
35. Spevacek AR, Evans EGB, Miller JL, Meyer HC, Pelton JG, Millhauser GL. Zinc drives a tertiary fold in the prion protein with familial disease mutation sites at the interface. Structure. 2013;21: 236–246. doi: 10.1016/j.str.2012.12.002 23290724
36. Tapella L, Stravalaci M, Bastone A, Biasini E, Gobbi M, Chiesa R. Epitope scanning indicates structural differences in brain-derived monomeric and aggregated mutant prion proteins related to genetic prion diseases. Biochem J. 2013;454: 417–25. doi: 10.1042/BJ20130563 23808898
37. Apetri AC, Vanik DL, Surewicz WK. Polymorphism at residue 129 modulates the conformational conversion of the D178N variant of human prion protein 90–231. Biochemistry. 2005;44: 15880–8. doi: 10.1021/bi051455+ 16313190
38. Biasini E, Tapella L, Restelli E, Pozzoli M, Massignan T, Chiesa R. The hydrophobic core region governs mutant prion protein aggregation and intracellular retention. Biochem J. 2010;430: 477–86. doi: 10.1042/BJ20100615 20626348
39. Daude N, Lehmann S, Harris DA. Identification of intermediate steps in the conversion of a mutant prion protein to a scrapie-like form in cultured cells. J Biol Chem. 1997;272: 11604–12. doi: 10.1074/jbc.272.17.11604 9111077
40. Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, et al. Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev. 2010;62: 405–96. doi: 10.1124/pr.109.002451 20716669
41. Sarnataro D, Campana V, Paladino S, Stornaiuolo M, Nitsch L, Zurzolo C. PrP C association with lipid rafts in the early secretory pathway stabilizes its cellular conformation. MBoC. 2004;15: 4031–4042. doi: 10.1091/mbc.e03-05-0271 15229281
42. Botto L, Cunati D, Coco S, Sesana S, Bulbarelli A, Biasini E, et al. Role of lipid rafts and GM1 in the segregation and processing of prion protein. PLoS One. 2014;9: e98344. doi: 10.1371/journal.pone.0098344 24859148
43. Isaac JT, Ashby MC, McBain CJ. The role of the GluR2 subunit in AMPA receptor function and synaptic plasticity. Neuron. 2007;54: 859–71. doi: 10.1016/j.neuron.2007.06.001 17582328
44. Ancona Esselmann SG, Díaz-Alonso J, Levy JM, Bemben MA, Nicoll RA. Synaptic homeostasis requires the membrane-proximal carboxy tail of GluA2. Proc Natl Acad Sci USA. 2017;114: 13266–13271. doi: 10.1073/pnas.1716022114 29180434
45. Pozo K, Goda Y. Unraveling mechanisms of homeostatic synaptic plasticity. Neuron. 2010;66: 337–351. doi: 10.1016/j.neuron.2010.04.028 20471348
46. Arundine M, Tymianski M. Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity. Cell Calcium. 2003;34: 325–337. doi: 10.1016/s0143-4160(03)00141-6 12909079
47. Kwak S, Weiss JH. Calcium-permeable AMPA channels in neurodegenerative disease and ischemia. Curr Opin Neurobiol. 2006;16: 281–287. doi: 10.1016/j.conb.2006.05.004 16698262
48. Liu SJ, Zukin RS. Ca2+-permeable AMPA receptors in synaptic plasticity and neuronal death. Trends Neurosci. 2007;30: 126–134. doi: 10.1016/j.tins.2007.01.006 17275103
49. Selvaraj BT, Livesey MR, Zhao C, Gregory JM, James OT, Cleary EM, et al. C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity. Nat Commun. 2018;9: 347. doi: 10.1038/s41467-017-02729-0 29367641
50. Rabenstein M, Peter F, Joost S, Trilck M, Rolfs A, Frech MJ. Decreased calcium flux in Niemann-Pick type C1 patient-specific iPSC-derived neurons due to higher amount of calcium-impermeable AMPA receptors. Mol Cell Neurosci. 2017;83: 27–36. doi: 10.1016/j.mcn.2017.06.007 28666962
51. Belichenko PV, Brown D, Jeffrey M, Fraser JR. Dendritic and synaptic alterations of hippocampal pyramidal neurones in scrapie-infected mice. Neuropathol Appl Neurobiol. 2000;26: 143–9. doi: 10.1046/j.1365-2990.2000.026002143.x 10840277
52. Chiesa R, Piccardo P, Quaglio E, Drisaldi B, Si-Hoe SL, Takao M, et al. Molecular distinction between pathogenic and infectious properties of the prion protein. J Virol. 2003;77: 7611–22. doi: 10.1128/jvi.77.13.7611-7622.2003 12805461
53. Chiesa R, Restelli E, Comerio L, Del Gallo F, Imeri L. Transgenic mice recapitulate the phenotypic heterogeneity of genetic prion diseases without developing prion infectivity: Role of intracellular PrP retention in neurotoxicity. Prion. 2016;10: 93–102. doi: 10.1080/19336896.2016.1139276 26864450
54. Hanley JG. AMPA receptor trafficking pathways and links to dendritic spine morphogenesis. Cell Adh Migr. 2008;2: 276–282. doi: 10.4161/cam.2.4.6510 19262155
55. Passafaro M, Nakagawa T, Sala C, Sheng M. Induction of dendritic spines by an extracellular domain of AMPA receptor subunit GluR2. Nature. 2003;424: 677–681. doi: 10.1038/nature01781 12904794
56. Um JW, Strittmatter SM. Amyloid-beta induced signaling by cellular prion protein and Fyn kinase in Alzheimer disease. Prion. 2013;7: 37–41. doi: 10.4161/pri.22212 22987042
57. Rutishauser D, Mertz KD, Moos R, Brunner E, Rulicke T, Calella AM, et al. The comprehensive native interactome of a fully functional tagged prion protein. PLoS One. 2009;4: e4446. doi: 10.1371/journal.pone.0004446 19209230
58. Bueler H, Fischer M, Lang Y, Bluethmann H, Lipp HP, DeArmond SJ, et al. Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature. 1992;356: 577–82. doi: 10.1038/356577a0 1373228
59. Restelli E, Fioriti L, Mantovani S, Airaghi S, Forloni G, Chiesa R. Cell type-specific neuroprotective activity of untranslocated prion protein. PLoS One. 2010;5: e13725. doi: 10.1371/journal.pone.0013725 21060848
60. Kascsak RJ, Rubenstein R, Merz PA, Tonna-DeMasi M, Fersko R, Carp RI, et al. Mouse polyclonal and monoclonal antibody to scrapie-associated fibril proteins. J Virol. 1987;61: 3688–93. 2446004
61. Rodriguez A, Ehlenberger DB, Dickstein DL, Hof PR, Wearne SL. Automated three-dimensional detection and shape classification of dendritic spines from fluorescence microscopy images. PLoS ONE. 2008;3: e1997. doi: 10.1371/journal.pone.0001997 18431482
62. Lehmann S, Harris DA. A mutant prion protein displays an aberrant membrane association when expressed in cultured cells. J Biol Chem. 1995;270: 24589–97. doi: 10.1074/jbc.270.41.24589 7592679
Článek vyšel v časopise
PLOS Pathogens
2020 Číslo 7
- Raději si zajděte na oční! Jak souvisí citlivost zraku s rozvojem demence?
- Může hubnutí souviset s vyšším rizikem nádorových onemocnění?
- Co způsobuje pooperační infekce? Na vině může být i naše vlastní mikrobiota
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Zkoušku z bariatrické chirurgie nejlépe složil ChatGPT-4. Za ním zůstaly Bing a Bard
Nejčtenější v tomto čísle
- Contained Mycobacterium tuberculosis infection induces concomitant and heterologous protection
- Protein phosphatase 1 catalyzes HBV core protein dephosphorylation and is co-packaged with viral pregenomic RNA into nucleocapsids
- Host prion protein expression levels impact prion tropism for the spleen
- Mutant prion proteins increase calcium permeability of AMPA receptors, exacerbating excitotoxicity