Aberrant association of misfolded SOD1 with Na+/K+ATPase-α3 impairs its activity and contributes to motor neuron vulnerability in ALS

详细信息    查看全文

• 作者：Céline Ruegsegger ; Niran Maharjan ; Anand Goswami…
• 关键词：ALS ; Na+/K+ATPase ; α3 ; SOD1 interactome ; Motor neuron excitability ; Sporadic and familial ALS
• 刊名：Acta Neuropathologica
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：131
• 期：3
• 页码：427-451
• 全文大小：4,205 KB
• 参考文献：1.Al Kaabi A, Traupe T, Stutz M, Buchs N, Heller M (2012) Cause or effect of arteriogenesis: compositional alterations of microparticles from CAD patients undergoing external counterpulsation therapy. PLoS One 7:e46822PubMedCentral CrossRef PubMed
  2.Andersen PM, Nilsson P, Ala-Hurula V, Keranen ML, Tarvainen I, Haltia T, Nilsson L, Binzer M, Forsgren L, Marklund SL (1995) Amyotrophic lateral sclerosis associated with homozygosity for an Asp90Ala mutation in CuZn-superoxide dismutase. Nat Genet 10:61–66CrossRef PubMed
  3.Atkin JD, Farg MA, Walker AK, McLean C, Tomas D, Horne MK (2008) Endoplasmic reticulum stress and induction of the unfolded protein response in human sporadic amyotrophic lateral sclerosis. Neurobiol Dis 30:400–407CrossRef PubMed
  4.Azarias G, Kruusmagi M, Connor S, Akkuratov EE, Liu XL, Lyons D, Brismar H, Broberger C, Aperia A (2013) A specific and essential role for Na, K-ATPase alpha3 in neurons co-expressing alpha1 and alpha3. J Biol Chem 288:2734–2743PubMedCentral CrossRef PubMed
  5.Bergh J, Zetterstrom P, Andersen PM, Brannstrom T, Graffmo KS, Jonsson PA, Lang L, Danielsson J, Oliveberg M, Marklund SL (2015) Structural and kinetic analysis of protein-aggregate strains in vivo using binary epitope mapping. Proc Natl Acad Sci USA 112:4489–4494. doi:10.​1073/​pnas.​1419228112 PubMedCentral CrossRef PubMed
  6.Berrow NS, Alderton D, Owens RJ (2009) The precise engineering of expression vectors using high-throughput In-Fusion PCR cloning. Methods Mol Biol 498:75–90. doi:10.​1007/​978-1-59745-196-3_​5 CrossRef PubMed
  7.Blanco G, Sanchez G, Mercer RW (1995) Comparison of the enzymatic properties of the Na, K-ATPase alpha 3 beta 1 and alpha 3 beta 2 isozymes. Biochemistry 34:9897–9903CrossRef PubMed
  8.Bories C, Amendola J, Lamotte d’Incamps B, Durand J (2007) Early electrophysiological abnormalities in lumbar motoneurons in a transgenic mouse model of amyotrophic lateral sclerosis. Eur J Neurosci 25:451–459CrossRef PubMed
  9.Bosco DA, Morfini G, Karabacak NM, Song Y, Gros-Louis F, Pasinelli P, Goolsby H, Fontaine BA, Lemay N, McKenna-Yasek D, Frosch MP, Agar JN, Julien JP, Brady ST, Brown RH Jr (2010) Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS. Nat Neurosci 13:1396–1403. doi:10.​1038/​nn.​2660 PubMedCentral CrossRef PubMed
  10.Chang Q, Martin LJ (2009) Glycinergic innervation of motoneurons is deficient in amyotrophic lateral sclerosis mice: a quantitative confocal analysis. Am J Pathol 174:574–585. doi:10.​2353/​ajpath.​2009.​080557 PubMedCentral CrossRef PubMed
  11.Costes SV, Daelemans D, Cho EH, Dobbin Z, Pavlakis G, Lockett S (2004) Automatic and quantitative measurement of protein-protein colocalization in live cells. Biophys J 86:3993–4003PubMedCentral CrossRef PubMed
  12.de Carvalho Aguiar P, Sweadner KJ, Penniston JT, Zaremba J, Liu L, Caton M, Linazasoro G, Borg M, Tijssen MA, Bressman SB, Dobyns WB, Brashear A, Ozelius LJ (2004) Mutations in the Na+/K+-ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism. Neuron 43:169–175CrossRef
  13.Devlin AC, Burr K, Borooah S, Foster JD, Cleary EM, Geti I, Vallier L, Shaw CE, Chandran S, Miles GB (2015) Human iPSC-derived motoneurons harbouring TARDBP or C9ORF72 ALS mutations are dysfunctional despite maintaining viability. Nat Commun 6:5999. doi:10.​1038/​ncomms6999 PubMedCentral CrossRef PubMed
  14.Dirren E, Towne CL, Setola V, Redmond DE Jr., Schneider BL, Aebischer P (2014) Intracerebroventricular injection of adeno-associated virus 6 and 9 vectors for cell type-specific transgene expression in the spinal cord. Hum Gene Ther 25:109–120CrossRef PubMed
  15.Dobretsov M, Stimers JR (2005) Neuronal function and alpha3 isoform of the Na/K-ATPase. Front Biosci 10:2373–2396CrossRef PubMed
  16.Ellis DZ, Rabe J, Sweadner KJ (2003) Global loss of Na, K-ATPase and its nitric oxide-mediated regulation in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurosci Off J Soc Neurosci 23:43–51
  17.Enjin A, Rabe N, Nakanishi ST, Vallstedt A, Gezelius H, Memic F, Lind M, Hjalt T, Tourtellotte WG, Bruder C, Eichele G, Whelan PJ, Kullander K (2010) Identification of novel spinal cholinergic genetic subtypes disclose Chodl and Pitx2 as markers for fast motor neurons and partition cells. J Comp Neurol 518:2284–2304CrossRef PubMed
  18.Ezzi SA, Urushitani M, Julien JP (2007) Wild-type superoxide dismutase acquires binding and toxic properties of ALS-linked mutant forms through oxidation. J Neurochem 102:170–178. doi:10.​1111/​j.​1471-4159.​2007.​04531.​x CrossRef PubMed
  19.Filezac de L’Etang A, Maharjan N, Cordeiro Brana M, Ruegsegger C, Rehmann R, Goswami A, Roos A, Troost D, Schneider BL, Weis J, Saxena S (2015) Marinesco-Sjogren syndrome protein SIL1 regulates motor neuron subtype-selective ER stress in ALS. Nat Neurosci. doi:10.​1038/​nn.​3903 PubMed
  20.Fraser CL, Arieff AI (2001) Na-K-ATPase activity decreases with aging in female rat brain synaptosomes. Am J Physiol Ren Physiol 281:F674–F678
  21.Fritz E, Izaurieta P, Weiss A, Mir FR, Rojas P, Gonzalez D, Rojas F, Brown RH Jr, Madrid R, van Zundert B (2013) Mutant SOD1-expressing astrocytes release toxic factors that trigger motoneuron death by inducing hyperexcitability. J Neurophysiol 109:2803–2814. doi:10.​1152/​jn.​00500.​2012 PubMedCentral CrossRef PubMed
  22.Gaudette M, Hirano M, Siddique T (2000) Current status of SOD1 mutations in familial amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1:83–89CrossRef PubMed
  23.Genet S, Kado RT (1997) Hyperpolarizing current of the Na/K ATPase contributes to the membrane polarization of the Purkinje cell in rat cerebellum. Pflugers Arch 434:559–567CrossRef PubMed
  24.Gros-Louis F, Soucy G, Lariviere R, Julien JP (2010) Intracerebroventricular infusion of monoclonal antibody or its derived Fab fragment against misfolded forms of SOD1 mutant delays mortality in a mouse model of ALS. J Neurochem 113:1188–1199PubMed
  25.Guareschi S, Cova E, Cereda C, Ceroni M, Donetti E, Bosco DA, Trotti D, Pasinelli P (2012) An over-oxidized form of superoxide dismutase found in sporadic amyotrophic lateral sclerosis with bulbar onset shares a toxic mechanism with mutant SOD1. Proc Natl Acad Sci USA 109:5074–5079. doi:10.​1073/​pnas.​1115402109 PubMedCentral CrossRef PubMed
  26.Gunasekera K, Wuthrich D, Braga-Lagache S, Heller M, Ochsenreiter T (2012) Proteome remodelling during development from blood to insect-form Trypanosoma brucei quantified by SILAC and mass spectrometry. BMC Genom 13:556CrossRef
  27.Gurney ME (1994) Transgenic-mouse model of amyotrophic lateral sclerosis. N Engl J Med 331:1721–1722CrossRef PubMed
  28.Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD, Caliendo J, Hentati A, Kwon YW, Deng HX et al (1994) Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science 264:1772–1775CrossRef PubMed
  29.Hegedus J, Putman CT, Tyreman N, Gordon T (2008) Preferential motor unit loss in the SOD1 G93A transgenic mouse model of amyotrophic lateral sclerosis. J Physiol 586:3337–3351PubMedCentral CrossRef PubMed
  30.Hieber V, Siegel GJ, Fink DJ, Beaty MW, Mata M (1991) Differential distribution of (Na, K)-ATPase alpha isoforms in the central nervous system. Cell Mol Neurobiol 11:253–262CrossRef PubMed
  31.Ilieva EV, Ayala V, Jove M, Dalfo E, Cacabelos D, Povedano M, Bellmunt MJ, Ferrer I, Pamplona R, Portero-Otin M (2007) Oxidative and endoplasmic reticulum stress interplay in sporadic amyotrophic lateral sclerosis. Brain 130:3111–3123CrossRef PubMed
  32.Inquimbert P, Moll M, Kohno T, Scholz J (2013) Stereotaxic injection of a viral vector for conditional gene manipulation in the mouse spinal cord. J Vis Exp 73:e50313. doi:10.​3791/​50313 PubMed
  33.Kreutz F, Scherer EB, Ferreira AG, Petry Fdos S, Pereira CL, Santana F, de Souza Wyse AT, Salbego CG, Trindade VM (2013) Alterations on Na(+), K(+)-ATPase and acetylcholinesterase activities induced by amyloid-beta peptide in rat brain and GM1 ganglioside neuroprotective action. Neurochem Res 38:2342–2350. doi:10.​1007/​s11064-013-1145-6 CrossRef PubMed
  34.Le Masson G, Przedborski S, Abbott LF (2014) A computational model of motor neuron degeneration. Neuron 83:975–988. doi:10.​1016/​j.​neuron.​2014.​07.​001 PubMedCentral CrossRef PubMed
  35.Leroy F, Lamotte d’Incamps B, Imhoff-Manuel RD, Zytnicki D (2014) Early intrinsic hyperexcitability does not contribute to motoneuron degeneration in amyotrophic lateral sclerosis. ELife 3. doi:10.​7554/​eLife.​04046
  36.Liguri G, Taddei N, Nassi P, Latorraca S, Nediani C, Sorbi S (1990) Changes in Na+, K(+)-ATPase, Ca2(+)-ATPase and some soluble enzymes related to energy metabolism in brains of patients with Alzheimer’s disease. Neurosci Lett 112:338–342CrossRef PubMed
  37.Lingrel JB (2010) The physiological significance of the cardiotonic steroid/ouabain-binding site of the Na, K-ATPase. Annu Rev Physiol 72:395–412PubMedCentral CrossRef PubMed
  38.Liu HN, Tjostheim S, Dasilva K, Taylor D, Zhao B, Rakhit R, Brown M, Chakrabartty A, McLaurin J, Robertson J (2012) Targeting of monomer/misfolded SOD1 as a therapeutic strategy for amyotrophic lateral sclerosis. J Neurosci Off J Soc Neurosci 32:8791–8799CrossRef
  39.Liu J, Lillo C, Jonsson PA, Vande Velde C, Ward CM, Miller TM, Subramaniam JR, Rothstein JD, Marklund S, Andersen PM, Brannstrom T, Gredal O, Wong PC, Williams DS, Cleveland DW (2004) Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondria. Neuron 43:5–17CrossRef PubMed
  40.Logroscino G, Traynor BJ, Hardiman O, Chio A, Mitchell D, Swingler RJ, Millul A, Benn E, Beghi E (2010) Incidence of amyotrophic lateral sclerosis in Europe. J Neurol Neurosurg Psychiatry 81:385–390PubMedCentral CrossRef PubMed
  41.Mark RJ, Hensley K, Butterfield DA, Mattson MP (1995) Amyloid beta-peptide impairs ion-motive ATPase activities: evidence for a role in loss of neuronal Ca2+ homeostasis and cell death. J Neurosci Off J Soc Neurosci 15:6239–6249
  42.McGrail KM, Phillips JM, Sweadner KJ (1991) Immunofluorescent localization of three Na, K-ATPase isozymes in the rat central nervous system: both neurons and glia can express more than one Na, K-ATPase. J Neurosci Off J Soc Neurosci 11:381–391
  43.Millul A, Beghi E, Logroscino G, Micheli A, Vitelli E, Zardi A (2005) Survival of patients with amyotrophic lateral sclerosis in a population-based registry. Neuroepidemiology 25:114–119CrossRef PubMed
  44.Munzer JS, Daly SE, Jewell-Motz EA, Lingrel JB, Blostein R (1994) Tissue- and isoform-specific kinetic behavior of the Na, K-ATPase. J Biol Chem 269:16668–16676PubMed
  45.Nishitoh H, Kadowaki H, Nagai A, Maruyama T, Yokota T, Fukutomi H, Noguchi T, Matsuzawa A, Takeda K, Ichijo H (2008) ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1. Genes Dev 22:1451–1464PubMedCentral CrossRef PubMed
  46.Pambo-Pambo A, Durand J, Gueritaud JP (2009) Early excitability changes in lumbar motoneurons of transgenic SOD1G85R and SOD1G(93A-Low) mice. J Neurophysiol 102:3627–3642CrossRef PubMed
  47.Piotrkiewicz M, Hausmanowa-Petrusewicz I (2011) Motoneuron afterhyperpolarisation duration in amyotrophic lateral sclerosis. J Physiol 589:2745–2754PubMedCentral CrossRef PubMed
  48.Pisani A, Martella G, Tscherter A, Costa C, Mercuri NB, Bernardi G, Shen J, Calabresi P (2006) Enhanced sensitivity of DJ-1-deficient dopaminergic neurons to energy metabolism impairment: role of Na+/K+ ATPase. Neurobiol Dis 23:54–60CrossRef PubMed
  49.Pullen AH, Athanasiou D (2009) Increase in presynaptic territory of C-terminals on lumbar motoneurons of G93A SOD1 mice during disease progression. Eur J Neurosci 29:551–561CrossRef PubMed
  50.Pun S, Santos AF, Saxena S, Xu L, Caroni P (2006) Selective vulnerability and pruning of phasic motoneuron axons in motoneuron disease alleviated by CNTF. Nat Neurosci 9:408–419CrossRef PubMed
  51.Puttaparthi K, Wojcik C, Rajendran B, DeMartino GN, Elliott JL (2003) Aggregate formation in the spinal cord of mutant SOD1 transgenic mice is reversible and mediated by proteasomes. J Neurochem 87:851–860CrossRef PubMed
  52.Rakhit R, Crow JP, Lepock JR, Kondejewski LH, Cashman NR, Chakrabartty A (2004) Monomeric Cu, Zn-superoxide dismutase is a common misfolding intermediate in the oxidation models of sporadic and familial amyotrophic lateral sclerosis. J Biol Chem 279:15499–15504CrossRef PubMed
  53.Rakhit R, Robertson J, Vande Velde C, Horne P, Ruth DM, Griffin J, Cleveland DW, Cashman NR, Chakrabartty A (2007) An immunological epitope selective for pathological monomer-misfolded SOD1 in ALS. Nat Med 13:754–759CrossRef PubMed
  54.Raoul C, Abbas-Terki T, Bensadoun JC, Guillot S, Haase G, Szulc J, Henderson CE, Aebischer P (2005) Lentiviral-mediated silencing of SOD1 through RNA interference retards disease onset and progression in a mouse model of ALS. Nat Med 11:423–428CrossRef PubMed
  55.Rotunno MS, Bosco DA (2013) An emerging role for misfolded wild-type SOD1 in sporadic ALS pathogenesis. Front Cell Neurosci 7:253. doi:10.​3389/​fncel.​2013.​00253 PubMedCentral CrossRef PubMed
  56.Saxena S, Cabuy E, Caroni P (2009) A role for motoneuron subtype-selective ER stress in disease manifestations of FALS mice. Nat Neurosci 12:627–636CrossRef PubMed
  57.Saxena S, Caroni P (2011) Selective neuronal vulnerability in neurodegenerative diseases: from stressor thresholds to degeneration. Neuron 71:35–48CrossRef PubMed
  58.Saxena S, Roselli F, Singh K, Leptien K, Julien JP, Gros-Louis F, Caroni P (2013) Neuroprotection through excitability and mTOR required in ALS motoneurons to delay disease and extend survival. Neuron 80:80–96CrossRef PubMed
  59.Schutz B (2005) Imbalanced excitatory to inhibitory synaptic input precedes motor neuron degeneration in an animal model of amyotrophic lateral sclerosis. Neurobiol Dis 20:131–140. doi:10.​1016/​j.​nbd.​2005.​02.​006 CrossRef PubMed
  60.Shinoda T, Ogawa H, Cornelius F, Toyoshima C (2009) Crystal structure of the sodium-potassium pump at 2.4 A resolution. Nature 459:446–450CrossRef PubMed
  61.Tortarolo M, Grignaschi G, Calvaresi N, Zennaro E, Spaltro G, Colovic M, Fracasso C, Guiso G, Elger B, Schneider H, Seilheimer B, Caccia S, Bendotti C (2006) Glutamate AMPA receptors change in motor neurons of SOD1G93A transgenic mice and their inhibition by a noncompetitive antagonist ameliorates the progression of amytrophic lateral sclerosis-like disease. J Neurosci Res 83:134–146. doi:10.​1002/​jnr.​20715 CrossRef PubMed
  62.Urayama O, Sweadner KJ (1988) Ouabain sensitivity of the alpha 3 isozyme of rat Na, K-ATPase. Biochem Biophys Res Commun 156:796–800CrossRef PubMed
  63.Urushitani M, Ezzi SA, Julien JP (2007) Therapeutic effects of immunization with mutant superoxide dismutase in mice models of amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 104:2495–2500PubMedCentral CrossRef PubMed
  64.Urushitani M, Ezzi SA, Matsuo A, Tooyama I, Julien JP (2008) The endoplasmic reticulum-Golgi pathway is a target for translocation and aggregation of mutant superoxide dismutase linked to ALS. FASEB J Off Publ Fed Am Soc Exp Biol 22:2476–2487
  65.Venugopal S, Hsiao CF, Sonoda T, Wiedau-Pazos M, Chandler SH (2015) Homeostatic dysregulation in membrane properties of masticatory motoneurons compared with oculomotor neurons in a mouse model for amyotrophic lateral sclerosis. J Neurosci Off J Soc Neurosci 35:707–720. doi:10.​1523/​JNEUROSCI.​1682-14.​2015 CrossRef
  66.Vucic S, Kiernan MC (2010) Upregulation of persistent sodium conductances in familial ALS. J Neurol Neurosurg Psychiatry 81:222–227CrossRef PubMed
  67.Vucic S, Nicholson GA, Kiernan MC (2008) Cortical hyperexcitability may precede the onset of familial amyotrophic lateral sclerosis. Brain 131:1540–1550CrossRef PubMed
  68.Wainger BJ, Kiskinis E, Mellin C, Wiskow O, Han SS, Sandoe J, Perez NP, Williams LA, Lee S, Boulting G, Berry JD, Brown RH Jr, Cudkowicz ME, Bean BP, Eggan K, Woolf CJ (2014) Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons. Cell Rep 7:1–11. doi:10.​1016/​j.​celrep.​2014.​03.​019 PubMedCentral CrossRef PubMed
  69.Wroe R, Wai-Ling Butler A, Andersen PM, Powell JF, Al-Chalabi A (2008) ALSOD: the amyotrophic lateral sclerosis online database. Amyotroph Lateral Scler 9:249–250CrossRef PubMed
  70.Zhang D, Hou Q, Wang M, Lin A, Jarzylo L, Navis A, Raissi A, Liu F, Man HY (2009) Na, K-ATPase activity regulates AMPA receptor turnover through proteasome-mediated proteolysis. J Neurosci Off J Soc Neurosci 29:4498–4511. doi:10.​1523/​JNEUROSCI.​6094-08.​2009 CrossRef
  
• 作者单位：Céline Ruegsegger (1) (2)
  Niran Maharjan (1) (2)
  Anand Goswami (3)
  Audrey Filézac de L’Etang (1) (2) (7)
  Joachim Weis (3)
  Dirk Troost (4)
  Manfred Heller (5)
  Heinz Gut (6)
  Smita Saxena (1)
  
  1. Institute of Cell Biology, University of Bern, Bern, Switzerland
  2. Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
  3. Institute of Neuropathology, Rheinisch-Westfälische Technische Hochschule, Aachen University Hospital, Aachen, Germany
  7. Department of Neuroscience, Genentech, Inc., South San Francisco, California, USA
  4. Division of Neuropathology, Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
  5. Department of Clinical Research, Inselspital, University of Bern, Bern, Switzerland
  6. Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Pathology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0533

文摘

Amyotrophic lateral sclerosis (ALS) is an adult onset progressive motor neuron disease with no cure. Transgenic mice overexpressing familial ALS associated human mutant SOD1 are a commonly used model for examining disease mechanisms. Presently, it is well accepted that alterations in motor neuron excitability and spinal circuits are pathological hallmarks of ALS, but the underlying molecular mechanisms remain unresolved. Here, we sought to understand whether the expression of mutant SOD1 protein could contribute to altering processes governing motor neuron excitability. We used the conformation specific antibody B8H10 which recognizes a misfolded state of SOD1 (misfSOD1) to longitudinally identify its interactome during early disease stage in SOD1G93A mice. This strategy identified a direct isozyme-specific association of misfSOD1 with Na+/K+ATPase-α3 leading to the premature impairment of its ATPase activity. Pharmacological inhibition of Na+/K+ATPase-α3 altered glutamate receptor 2 expression, modified cholinergic inputs and accelerated disease pathology. After mapping the site of direct association of misfSOD1 with Na+/K+ATPase-α3 onto a 10 amino acid stretch that is unique to Na+/K+ATPase-α3 but not found in the closely related Na+/K+ATPase-α1 isozyme, we generated a misfSOD1 binding deficient, but fully functional Na+/K+ATPase-α3 pump. Adeno associated virus (AAV)-mediated expression of this chimeric Na+/K+ATPase-α3 restored Na+/K+ATPase-α3 activity in the spinal cord, delayed pathological alterations and prolonged survival of SOD1G93A mice. Additionally, altered Na+/K+ATPase-α3 expression was observed in the spinal cord of individuals with sporadic and familial ALS. A fraction of sporadic ALS cases also presented B8H10 positive misfSOD1 immunoreactivity, suggesting that similar mechanism might contribute to the pathology. Keywords ALS Na+/K+ATPase-α3 SOD1 interactome Motor neuron excitability Sporadic and familial ALS