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Pathogenic Tau Causes a Toxic Depletion of Nuclear Calcium

Mahoney, Rebekah, Ochoa Thomas, Elizabeth, Ramirez, Paulino, Miller, Henry E., Beckmann, Adrian, Zuniga, Gabrielle, Dobrowolski, Radek, Frost, Bess·2020·Cell Reports
DOI 10.1016/j.celrep.2020.107900PMC PMC7428851
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Figure 1. TauR406W Causes Reduction of Nuclear CREB in Neurons of the Adult Drosophila Brain (A) CREB protein levels in control and tauR406W transgenic Drosophila head lysates based on western blotting, n = 6 biological replicates. (B) CREB and elav immunostaining in the mushroom body of control and tauR406W transgenic Drosophila visualized by confocal microscopy. Images are from a single focal plane. n = 5 biological replicates. Scale bar, 5 μm. (C) CREB and elav immunostaining in the mushroom body of control and tauR406W transgenic Drosophila visualized by confocal microscopy. Images are from a single focal plane. Elav-based masks (represented by white outlines) were used to measure nuclear CREB levels, n = 5 biological replicates. Scale bar, 5 mm. All assays were performed at day 10 of adulthood. Data are presented as mean ± SEM; unpaired t test; *p < 0.05, **p < 0.01, ***p < 0.001.
Figure 1. TauR406W Causes Reduction of Nuclear CREB in Neurons of the Adult Drosophila Brain (A) CREB protein levels in control and tauR406W transgenic Drosophila head lysates based on western blotting, n = 6 biological replicates. (B) CREB and elav immunostaining in the mushroom body of control and tauR406W transgenic Drosophila visualized by confocal microscopy. Images are from a single focal plane. n = 5 biological replicates. Scale bar, 5 μm. (C) CREB and elav immunostaining in the mushroom body of control and tauR406W transgenic Drosophila visualized by confocal microscopy. Images are from a single focal plane. Elav-based masks (represented by white outlines) were used to measure nuclear CREB levels, n = 5 biological replicates. Scale bar, 5 mm. All assays were performed at day 10 of adulthood. Data are presented as mean ± SEM; unpaired t test; *p < 0.05, **p < 0.01, ***p < 0.001.CC BY-NC-ND · PubMed Central
Figure 2. TauR406W Transgenic Drosophila Have a Toxic Reduction of Nuclear Ca2+ (A) Activation of the nuclear Ca2+ reporter in the mushroom body of the adult Drosophila brain based on GCaMP3.NLS in vivo imaging. (B) Decreased levels of nuclear Ca2+ in the mushroom body of the tauR406W transgenic Drosophila brain versus control based on GCaMP3.NLS in vivo imaging. Images are of a single focal plane. Scale bar, 60 μm (C) Quantification of nuclear Ca2+ based on GCaMP3.NLS in control and tauR406W transgenic Drosophila of the indicated age. n = 6–8 biological replicates per genotype, per age. Data are presented as mean ± SD. For visual simplicity, significance is only noted for differences between genotypes at each age. Statistical analyses of the age-dependent decline in nuclear Ca2+ within each genotype are presented in Figures S1C and S1D. (D) Neurodegeneration assayed by TUNEL staining in brains of control and tauR406W transgenic Drosophila with and without nuclear Ca2+ blockage via panneuronal overexpression of CaMBP4. All assays were performed at day 10 of adulthood with the exception of (C). Data are presented as mean ± SEM unless otherwise noted. One-way ANOVA with Tukey’s multiple comparison test; ***p < 0.001, ****p < 0.0001.
Figure 2. TauR406W Transgenic Drosophila Have a Toxic Reduction of Nuclear Ca2+ (A) Activation of the nuclear Ca2+ reporter in the mushroom body of the adult Drosophila brain based on GCaMP3.NLS in vivo imaging. (B) Decreased levels of nuclear Ca2+ in the mushroom body of the tauR406W transgenic Drosophila brain versus control based on GCaMP3.NLS in vivo imaging. Images are of a single focal plane. Scale bar, 60 μm (C) Quantification of nuclear Ca2+ based on GCaMP3.NLS in control and tauR406W transgenic Drosophila of the indicated age. n = 6–8 biological replicates per genotype, per age. Data are presented as mean ± SD. For visual simplicity, significance is only noted for differences between genotypes at each age. Statistical analyses of the age-dependent decline in nuclear Ca2+ within each genotype are presented in Figures S1C and S1D. (D) Neurodegeneration assayed by TUNEL staining in brains of control and tauR406W transgenic Drosophila with and without nuclear Ca2+ blockage via panneuronal overexpression of CaMBP4. All assays were performed at day 10 of adulthood with the exception of (C). Data are presented as mean ± SEM unless otherwise noted. One-way ANOVA with Tukey’s multiple comparison test; ***p < 0.001, ****p < 0.0001.CC BY-NC-ND · PubMed Central
Figure 3. KCl-Induced Nuclear Ca2+ Influx Is Reduced in Brains of TauR406W Transgenic Drosophila and in iPSC-Derived Neurons from Sporadic Cases of Human Alzheimer’s Disease (A) Decreased depolarization-dependent influx of nuclear Ca2+ in tauR406W transgenic Drosophila compared to control in response to administration of 70 mM KCl through a cuticular window in heads of living Drosophila. (B) Quantification of the area under the curve from (A), n = 6 biological replicates. (C) Decreased KCl-induced release of nuclear Ca2+ in iPSC-derived neurons from patients with Alzheimer’s disease. Cells were transfected with membrane-bound RFP and the GCaMP6s.NLS nuclear Ca2+ reporter. Images show peak nuclear Ca2+ levels induced by 25 mM KCl. Images are from a single focal plane. Scale bar, 10 μm. (D) Quantification of (C). Data are presented as peak ΔF/F0, in which ΔF is the change in GCaMP6s.NLS GFP fluorescence, and F0 is baseline GFP fluorescence. Nuclear Ca2+ was quantified in at least 50 single cells for each of six technical replicates per human sample. iPSC-derived neurons are from two control and three sporadic Alzheimer’s disease patients. All assays in Drosophila were performed at day 10 of adulthood. Data are presented as the mean ± SEM; unpaired t test or ANOVA; **p < 0.01, ***p < 0.001.
Figure 3. KCl-Induced Nuclear Ca2+ Influx Is Reduced in Brains of TauR406W Transgenic Drosophila and in iPSC-Derived Neurons from Sporadic Cases of Human Alzheimer’s Disease (A) Decreased depolarization-dependent influx of nuclear Ca2+ in tauR406W transgenic Drosophila compared to control in response to administration of 70 mM KCl through a cuticular window in heads of living Drosophila. (B) Quantification of the area under the curve from (A), n = 6 biological replicates. (C) Decreased KCl-induced release of nuclear Ca2+ in iPSC-derived neurons from patients with Alzheimer’s disease. Cells were transfected with membrane-bound RFP and the GCaMP6s.NLS nuclear Ca2+ reporter. Images show peak nuclear Ca2+ levels induced by 25 mM KCl. Images are from a single focal plane. Scale bar, 10 μm. (D) Quantification of (C). Data are presented as peak ΔF/F0, in which ΔF is the change in GCaMP6s.NLS GFP fluorescence, and F0 is baseline GFP fluorescence. Nuclear Ca2+ was quantified in at least 50 single cells for each of six technical replicates per human sample. iPSC-derived neurons are from two control and three sporadic Alzheimer’s disease patients. All assays in Drosophila were performed at day 10 of adulthood. Data are presented as the mean ± SEM; unpaired t test or ANOVA; **p < 0.01, ***p < 0.001.CC BY-NC-ND · PubMed Central
Figure 4. BK Channels Modify Nuclear Ca2+ Release and Neurotoxicity in TauR406W Transgenic Drosophila (A) Visualization of nuclear Ca2+ based on in vivo imaging of GCaMP3.NLS in tauR406W transgenic Drosophila fed either vehicle or BMS-191011 from days 2–10 of adulthood. Images are from a single focal plane. Scale bar, 10 μm. (B) Quantification of (A), n = 6 biological replicates. (C) Neurodegeneration assayed by TUNEL staining in the brains of control and tauR406W transgenic Drosophila with and without exposure to BMS-191011 from days 2–10 of adulthood, n = 6 biological replicates. (D) Neurodegeneration assayed by TUNEL staining in the brains of control and tauR406W transgenic Drosophila with and without RNAi-mediated depletion or loss-of-function of slowpoke; n = 6 biological replicates. All assays were performed at day 10 of adulthood. Data are presented as mean ± SEM; unpaired t test or ANOVA; *p < 0.05, ****p < 0.0001.
Figure 4. BK Channels Modify Nuclear Ca2+ Release and Neurotoxicity in TauR406W Transgenic Drosophila (A) Visualization of nuclear Ca2+ based on in vivo imaging of GCaMP3.NLS in tauR406W transgenic Drosophila fed either vehicle or BMS-191011 from days 2–10 of adulthood. Images are from a single focal plane. Scale bar, 10 μm. (B) Quantification of (A), n = 6 biological replicates. (C) Neurodegeneration assayed by TUNEL staining in the brains of control and tauR406W transgenic Drosophila with and without exposure to BMS-191011 from days 2–10 of adulthood, n = 6 biological replicates. (D) Neurodegeneration assayed by TUNEL staining in the brains of control and tauR406W transgenic Drosophila with and without RNAi-mediated depletion or loss-of-function of slowpoke; n = 6 biological replicates. All assays were performed at day 10 of adulthood. Data are presented as mean ± SEM; unpaired t test or ANOVA; *p < 0.05, ****p < 0.0001.CC BY-NC-ND · PubMed Central

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Research works printed but not linked: 38

  1. Ambrosini, 2003, Signal search analysis server, Nucleic Acids Res., 31, 3618, 10.1093/nar/gkg611 · doi:10.1093/nar/gkg611
  2. Ashburner, 2000, Gene ontology: tool for the unification of biology, Nat. Genet., 25, 25, 10.1038/75556 · DOI · Paper page
  3. Bading, 2013, Nuclear calcium signalling in the regulation of brain function, Nat. Rev. Neurosci., 14, 593, 10.1038/nrn3531 · DOI · Paper page
  4. Bartolotti, 2016, Reduced pCREB in Alzheimer’s disease prefrontal cortex is reflected in peripheral blood mononuclear cells, Mol. Psychiatry, 21, 1158, 10.1038/mp.2016.111 · DOI
  5. Benito, 2010, CREB’s control of intrinsic and synaptic plasticity: implications for CREB-dependent memory models, Trends Neurosci., 33, 230, 10.1016/j.tins.2010.02.001 · DOI · Paper page
  6. Bjorklund, 2012, Absence of amyloid β oligomers at the postsynapse and regulated synaptic Zn2+ in cognitively intact aged individuals with Alzheimer’s disease neuropathology, Mol. Neurodegener., 7, 23, 10.1186/1750-1326-7-23 · DOI · Paper page
  7. Bolger, 2014, Trimmomatic: a flexible trimmer for Illumina sequence data, Bioinformatics, 30, 2114, 10.1093/bioinformatics/btu170 · DOI · Paper page
  8. Bucher, 1986, Compilation and analysis of eukaryotic POL II promoter sequences, Nucleic Acids Res., 14, 10009, 10.1093/nar/14.24.10009 · DOI · Paper page
  9. Chambers, 2009, Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling, Nat. Biotechnol., 27, 275, 10.1038/nbt.1529 · DOI · Paper page
  10. Edgar, 2002, Gene Expression Omnibus: NCBI gene expression and hybridization array data repository, Nucleic Acids Res., 30, 207, 10.1093/nar/30.1.207 · DOI · Paper page
  11. Fiala, 2003, In vivo calcium imaging of brain activity in Drosophila by transgenic cameleon expression, Sci. STKE, 2003, PL6, 10.1126/stke.2003.174.pl6 · DOI
  12. Forrest, 2018, Retiring the term FTDP-17 as MAPT mutations are genetic forms of sporadic frontotemporal tauopathies, Brain, 141, 521, 10.1093/brain/awx328 · DOI
  13. Hagenston, 2011, Calcium signaling in synapse-to-nucleus communication, Cold Spring Harb. Perspect. Biol., 3, a004564, 10.1101/cshperspect.a004564 · DOI
  14. Hardingham, 2001, Nuclear calcium signaling controls CREB-mediated gene expression triggered by synaptic activity, Nat. Neurosci., 4, 261, 10.1038/85109 · DOI · Paper page
  15. Heisenberg, 2003, Mushroom body memoir: from maps to models, Nat. Rev. Neurosci., 4, 266, 10.1038/nrn1074 · DOI · Paper page
  16. Hirano, 2016, Shifting transcriptional machinery is required for long-term memory maintenance and modification in Drosophila mushroom bodies, Nat. Commun., 7, 13471, 10.1038/ncomms13471 · DOI
  17. Hutton, 1998, Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17, Nature, 393, 702, 10.1038/31508 · DOI · Paper page
  18. Khurana, 2012, A neuroprotective role for the DNA damage checkpoint in tauopathy, Aging Cell, 11, 360, 10.1111/j.1474-9726.2011.00778.x · DOI
  19. Li, 2014, Nuclear BK channels regulate gene expression via the control of nuclear calcium signaling, Nat. Neurosci., 17, 1055, 10.1038/nn.3744 · DOI
  20. Love, 2014, Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2, Genome Biol., 15, 550, 10.1186/s13059-014-0550-8 · DOI · Paper page
  21. Mahoney, 2014, An age-dependent change in the set point of synaptic homeostasis, J. Neurosci., 34, 2111, 10.1523/JNEUROSCI.3556-13.2014 · DOI
  22. Merlo, 2014, p53 prevents neurodegeneration by regulating synaptic genes, Proc. Natl. Acad. Sci. USA, 111, 18055, 10.1073/pnas.1419083111 · DOI
  23. Nakai, 2001, A high signal-to-noise Ca(2+) probe composed of a single green fluorescent protein, Nat. Biotechnol., 19, 137, 10.1038/84397 · DOI · Paper page
  24. Oddo, 2003, Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction, Neuron, 39, 409, 10.1016/S0896-6273(03)00434-3 · DOI · Paper page
  25. Patro, 2017, Salmon provides fast and bias-aware quantification of transcript expression, Nat. Methods, 14, 417, 10.1038/nmeth.4197 · DOI · Paper page
  26. Pugazhenthi, 2011, Downregulation of CREB expression in Alzheimer’s brain and in Aβ-treated rat hippocampal neurons, Mol. Neurodegener., 6, 60, 10.1186/1750-1326-6-60 · DOI · Paper page
  27. Reddy, 2016, Dysregulation of Nutrient Sensing and CLEARance in Presenilin Deficiency, Cell Rep., 14, 2166, 10.1016/j.celrep.2016.02.006 · DOI
  28. Sproul, 2014, Characterization and molecular profiling of PSEN1 familial Alzheimer’s disease iPSC-derived neural progenitors, PLoS ONE, 9, e84547, 10.1371/journal.pone.0084547 · DOI · Paper page
  29. Thurmond, 2019, FlyBase 2.0: the next generation, Nucleic Acids Res., 47, D759, 10.1093/nar/gky1003 · DOI · Paper page
  30. Uddin, 2018, Autophagy and Alzheimer’s Disease: From Molecular Mechanisms to Therapeutic Implications, Front. Aging Neurosci., 10, 04, 10.3389/fnagi.2018.00004 · DOI · Paper page
  31. Usui, 1993, Isolation of Drosophila CREB-B: a novel CRE-binding protein, DNA Cell Biol., 12, 589, 10.1089/dna.1993.12.589 · doi:10.1089/dna.1993.12.589
  32. Wang, 2015, Improvement of spatial learning by facilitating large-conductance calcium-activated potassium channel with transcranial magnetic stimulation in Alzheimer’s disease model mice, Neuropharmacology, 97, 210, 10.1016/j.neuropharm.2015.05.027 · DOI
  33. Wang, 2015, Cognitive recovery by chronic activation of the large-conductance calcium-activated potassium channel in a mouse model of Alzheimer’s disease, Neuropharmacology, 92, 8, 10.1016/j.neuropharm.2014.12.033 · DOI
  34. Weislogel, 2013, Requirement for nuclear calcium signaling in Drosophila long-term memory, Sci. Signal., 6, ra33, 10.1126/scisignal.2003598 · DOI
  35. Yin, 1995, A Drosophila CREB/CREM homolog encodes multiple isoforms, including a cyclic AMP-dependent protein kinase-responsive transcriptional activator and antagonist, Mol. Cell. Biol., 15, 5123, 10.1128/MCB.15.9.5123 · DOI
  36. Yin, 2016, Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling, Proc. Natl. Acad. Sci. USA, 113, E3773, 10.1073/pnas.1604519113 · DOI · Paper page
  37. Zhang, 2009, Nuclear calcium signaling controls expression of a large gene pool: identification of a gene program for acquired neuroprotection induced by synaptic activity, PLoS Genet., 5, e1000604, 10.1371/journal.pgen.1000604 · DOI · Paper page
  38. Zhu, 2010, ChIPpeakAnno: a Bioconductor package to annotate ChIP-seq and ChIP-chip data, BMC Bioinformatics, 11, 237, 10.1186/1471-2105-11-237 · DOI · Paper page

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Metadata

Authors
Mahoney, R., Ochoa Thomas, E., Ramirez, P., Miller, H. E., Beckmann, A., Zuniga, G., Dobrowolski, R., & Frost, B.
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2020-07
Volume
32
Issue
2
Pages
107900
ISSN
2211-1247
DOI
10.1016/j.celrep.2020.107900
PMC
PMC7428851
Cited by
31
References
9
Language
en
Licence
Funders
  • National Institute on Aging
  • National Institute of General Medical Sciences
  • American Federation for Aging Research

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Mahoney, R., Ochoa Thomas, E., Ramirez, P., Miller, H. E., Beckmann, A., Zuniga, G., Dobrowolski, R., & Frost, B. (2020). Pathogenic Tau Causes a Toxic Depletion of Nuclear Calcium. Cell Reports. https://doi.org/10.1016/j.celrep.2020.107900

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