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Impaired JIP3-dependent axonal lysosome transport promotes amyloid plaque pathology

Gowrishankar, Swetha, Wu, Yumei, Ferguson, Shawn M.·2017·Journal of Cell Biology
DOI 10.1083/jcb.201612148PMC PMC5626538
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Abstract

Lysosomes robustly accumulate within axonal swellings at Alzheimer’s disease (AD) amyloid plaques. However, the underlying mechanisms and disease relevance of such lysosome accumulations are not well understood. Motivated by these problems, we identified JNK-interacting protein 3 (JIP3) as an important regulator of axonal lysosome transport and maturation. JIP3 knockout mouse neuron primary cultures accumulate lysosomes within focal axonal swellings that resemble the dystrophic axons at amyloid plaques. These swellings contain high levels of amyloid precursor protein processing enzymes (BACE1 and presenilin 2) and are accompanied by elevated Aβ peptide levels. The in vivo importance of the JIP3-dependent regulation of axonal lysosomes was revealed by the worsening of the amyloid plaque pathology arising from JIP3 haploinsufficiency in a mouse model of AD. These results establish the critical role of JIP3-dependent axonal lysosome transport in regulating amyloidogenic amyloid precursor protein processing and support a model wherein Aβ production is amplified by plaque-induced axonal lysosome transport defects.

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  • Mouse studies indicate that lysosomal accumulation in dystrophic axons arises from impaired retrograde axonal transport and lysosomal maturation, rather than increased anterograde trafficking, which enhances amyloidogenic APP processing by limiting lysosomal degradation.

    “Mouse studies indicate this arises from impaired retrograde axonal transport and lysosomal maturation, rather than increased anterograde trafficking, which enhances amyloidogenic APP processing by limiting lysosomal degradation (Gowrishankar et al. 2015;Gowrishankar et al. 2017).”

    From TMEM55B downregulation promotes neurodegeneration in Alzheimer’s disease models (2026) · cites this paper as Gowrishankar et al. 2017

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Research works printed but not linked: 52

  1. Allison, 2017, Defects in ER–endosome contacts impact lysosome function in hereditary spastic paraplegia, J. Cell Biol., 216, 1337, 10.1083/jcb.201609033 · DOI · Paper page
  2. Annaert, 1999, Presenilin 1 controls gamma-secretase processing of amyloid precursor protein in pre-golgi compartments of hippocampal neurons, J. Cell Biol., 147, 277, 10.1083/jcb.147.2.277 · DOI
  3. Area-Gomez, 2009, Presenilins are enriched in endoplasmic reticulum membranes associated with mitochondria, Am. J. Pathol., 175, 1810, 10.2353/ajpath.2009.090219 · DOI · Paper page
  4. Arimoto, 2011, The Caenorhabditis elegans JIP3 protein UNC-16 functions as an adaptor to link kinesin-1 with cytoplasmic dynein, J. Neurosci., 31, 2216, 10.1523/JNEUROSCI.2653-10.2011 · DOI
  5. Brown, 2009, The JIP3 scaffold protein UNC-16 regulates RAB-5 dependent membrane trafficking at C. elegans synapses, Dev. Neurobiol., 69, 174, 10.1002/dneu.20690 · DOI
  6. Cai, 2010, Snapin-regulated late endosomal transport is critical for efficient autophagy-lysosomal function in neurons, Neuron., 68, 73, 10.1016/j.neuron.2010.09.022 · DOI · Paper page
  7. Cataldo, 1994, Lysosomal abnormalities in degenerating neurons link neuronal compromise to senile plaque development in Alzheimer disease, Brain Res., 640, 68, 10.1016/0006-8993(94)91858-9 · DOI · Paper page
  8. Cavalli, 2005, Sunday Driver links axonal transport to damage signaling, J. Cell Biol., 168, 775, 10.1083/jcb.200410136 · DOI
  9. Cheng, 2015, Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes, J. Cell Biol., 209, 377, 10.1083/jcb.201412046 · DOI
  10. Condello, 2011, Multicolor time-stamp reveals the dynamics and toxicity of amyloid deposition, Sci. Rep., 1, 19, 10.1038/srep00019 · DOI
  11. Cras, 1991, Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein, Proc. Natl. Acad. Sci. USA., 88, 7552, 10.1073/pnas.88.17.7552 · DOI
  12. Cummings, 1992, Aggregation of the amyloid precursor protein within degenerating neurons and dystrophic neurites in Alzheimer’s disease, Neuroscience., 48, 763, 10.1016/0306-4522(92)90265-4 · DOI · Paper page
  13. Cupers, 2001, The discrepancy between presenilin subcellular localization and gamma-secretase processing of amyloid precursor protein, J. Cell Biol., 154, 731, 10.1083/jcb.200104045 · DOI
  14. Das, 2016, Visualizing APP and BACE-1 approximation in neurons yields insight into the amyloidogenic pathway, Nat. Neurosci., 19, 55, 10.1038/nn.4188 · DOI
  15. Dikranian, 2012, Ultrastructural studies in APP/PS1 mice expressing human ApoE isoforms: Implications for Alzheimer’s disease, Int. J. Clin. Exp. Pathol., 5, 482
  16. Drerup, 2013, JNK-interacting protein 3 mediates the retrograde transport of activated c-Jun N-terminal kinase and lysosomes, PLoS Genet., 9, e1003303, 10.1371/journal.pgen.1003303 · DOI
  17. Edwards, 2013, An organelle gatekeeper function for Caenorhabditis elegans UNC-16 (JIP3) at the axon initial segment, Genetics., 194, 143, 10.1534/genetics.112.147348 · DOI · Paper page
  18. Ewers, 2008, Increased CSF-BACE 1 activity is associated with ApoE-ε4 genotype in subjects with mild cognitive impairment and Alzheimer’s disease, Brain., 131, 1252, 10.1093/brain/awn034 · DOI · Paper page
  19. Farías, 2017, BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon, Proc. Natl. Acad. Sci. USA., 114, E2955, 10.1073/pnas.1616363114 · DOI · Paper page
  20. Fiala, 2007, Mechanisms of amyloid plaque pathogenesis, Acta Neuropathol., 114, 551, 10.1007/s00401-007-0284-8 · DOI
  21. Gentleman, 1993, β-amyloid precursor protein (β APP) as a marker for axonal injury after head injury, Neurosci. Lett., 160, 139, 10.1016/0304-3940(93)90398-5 · DOI
  22. Gowrishankar, 2015, Massive accumulation of luminal protease-deficient axonal lysosomes at Alzheimer’s disease amyloid plaques, Proc. Natl. Acad. Sci. USA., 112, E3699, 10.1073/pnas.1510329112 · DOI · Paper page
  23. Hollenbeck, 1993, Products of endocytosis and autophagy are retrieved from axons by regulated retrograde organelle transport, J. Cell Biol., 121, 305, 10.1083/jcb.121.2.305 · DOI
  24. Huang, 2011, JIP3 mediates TrkB axonal anterograde transport and enhances BDNF signaling by directly bridging TrkB with kinesin-1, J. Neurosci., 31, 10602, 10.1523/JNEUROSCI.0436-11.2011 · DOI
  25. Jordens, 2001, The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein-dynactin motors, Curr. Biol., 11, 1680, 10.1016/S0960-9822(01)00531-0 · DOI · Paper page
  26. Kelkar, 2003, Morphogenesis of the telencephalic commissure requires scaffold protein JNK-interacting protein 3 (JIP3), Proc. Natl. Acad. Sci. USA., 100, 9843, 10.1073/pnas.1733944100 · DOI
  27. Kim, 2000, Subcellular localization of presenilins: association with a unique membrane pool in cultured cells, Neurobiol. Dis., 7, 99, 10.1006/nbdi.1999.0280 · DOI
  28. Kovacs, 1996, Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells, Nat. Med., 2, 224, 10.1038/nm0296-224 · DOI
  29. Maday, 2014, Autophagosome biogenesis in primary neurons follows an ordered and spatially regulated pathway, Dev. Cell., 30, 71, 10.1016/j.devcel.2014.06.001 · DOI · Paper page
  30. Montagnac, 2009, ARF6 interacts with JIP4 to control a motor switch mechanism regulating endosome traffic in cytokinesis, Curr. Biol., 19, 184, 10.1016/j.cub.2008.12.043 · DOI · Paper page
  31. Nixon, 2005, Extensive involvement of autophagy in Alzheimer disease: An immuno-electron microscopy study, J. Neuropathol. Exp. Neurol., 64, 113, 10.1093/jnen/64.2.113 · DOI · Paper page
  32. Overly, 1995, Quantitative measurement of intraorganelle pH in the endosomal-lysosomal pathway in neurons by using ratiometric imaging with pyranine, Proc. Natl. Acad. Sci. USA., 92, 3156, 10.1073/pnas.92.8.3156 · DOI
  33. Pasternak, 2003, Presenilin-1, nicastrin, amyloid precursor protein, and gamma-secretase activity are co-localized in the lysosomal membrane, J. Biol. Chem., 278, 26687, 10.1074/jbc.M304009200 · DOI
  34. Pu, 2015, BORC, a multisubunit complex that regulates lysosome positioning, Dev. Cell., 33, 176, 10.1016/j.devcel.2015.02.011 · DOI · Paper page
  35. Pu, 2016, Mechanisms and functions of lysosome positioning, J. Cell Sci., 129, 4329, 10.1242/jcs.196287 · DOI · Paper page
  36. Roberts, 1991, β A4 amyloid protein deposition in brain after head trauma, Lancet., 338, 1422, 10.1016/0140-6736(91)92724-G · DOI
  37. Rowland, 2014, ER contact sites define the position and timing of endosome fission, Cell., 159, 1027, 10.1016/j.cell.2014.10.023 · DOI
  38. Sannerud, 2016, Restricted location of PSEN2/γ-secretase determines substrate specificity and generates an intracellular Aβ pool, Cell., 166, 193, 10.1016/j.cell.2016.05.020 · DOI · Paper page
  39. Sato, 2015, JSAP1/JIP3 and JLP regulate kinesin-1-dependent axonal transport to prevent neuronal degeneration, Cell Death Differ., 22, 1260, 10.1038/cdd.2014.207 · DOI
  40. Sherriff, 1994, Early detection of axonal injury after human head trauma using immunocytochemistry for β-amyloid precursor protein, Acta Neuropathol., 87, 55, 10.1007/BF00386254 · DOI
  41. Stokin, 2005, Axonopathy and transport deficits early in the pathogenesis of Alzheimer’s disease, Science., 307, 1282, 10.1126/science.1105681 · DOI · Paper page
  42. Su, 1993, Identification and distribution of axonal dystrophic neurites in Alzheimer’s disease, Brain Res., 625, 228, 10.1016/0006-8993(93)91063-X · DOI
  43. Sun, 2011, Sunday Driver/JIP3 binds kinesin heavy chain directly and enhances its motility, EMBO J., 30, 3416, 10.1038/emboj.2011.229 · DOI
  44. Teich, 2013, A reliable way to detect endogenous murine β-amyloid, PLoS One., 8, e55647, 10.1371/journal.pone.0055647 · DOI
  45. Terry, 1964, Ultrastructural studies in Alzheimer’s presenile dementia, Am. J. Pathol., 44, 269
  46. Tran, 2011, Controlled cortical impact traumatic brain injury in 3xTg-AD mice causes acute intra-axonal amyloid-β accumulation and independently accelerates the development of τ abnormalities, J. Neurosci., 31, 9513, 10.1523/JNEUROSCI.0858-11.2011 · DOI · Paper page
  47. Wu, 2014, A dynamin 1-, dynamin 3- and clathrin-independent pathway of synaptic vesicle recycling mediated by bulk endocytosis, eLife, 3, e01621, 10.7554/eLife.01621 · DOI
  48. Ye, 2017, Regulation of synaptic amyloid-β generation through BACE1 retrograde transport in a mouse model of Alzheimer’s disease, J. Neurosci., 37, 2639, 10.1523/JNEUROSCI.2851-16.2017 · DOI
  49. Yoon, 2013, α-secretase cleaved amyloid precursor protein (APP) accumulates in cholinergic dystrophic neurites in normal, aged hippocampus, Neuropathol. Appl. Neurobiol., 39, 800, 10.1111/nan.12032 · DOI
  50. Yu, 2005, Macroautophagy—A novel β-amyloid peptide-generating pathway activated in Alzheimer’s disease, J. Cell Biol., 171, 87, 10.1083/jcb.200505082 · DOI · Paper page
  51. Yuan, 2016, TREM2 haplodeficiency in mice and humans impairs the microglia barrier function leading to decreased amyloid compaction and severe axonal dystrophy, Neuron., 90, 724, 10.1016/j.neuron.2016.05.003 · DOI · Paper page
  52. Zhao, 2007, β-site amyloid precursor protein cleaving enzyme 1 levels become elevated in neurons around amyloid plaques: Implications for Alzheimer’s disease pathogenesis, J. Neurosci., 27, 3639, 10.1523/JNEUROSCI.4396-06.2007 · DOI · Paper page

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Metadata

Authors
Gowrishankar, S., Wu, Y., & Ferguson, S. M.
Affiliations
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 1
ORCID
Ferguson, Shawn M.
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2017-08-07
Volume
216
Issue
10
Pages
3291-3305
ISSN
  • 0021-9525
  • 1540-8140
DOI
10.1083/jcb.201612148
PMC
PMC5626538
Cited by
138
References
11
Language
en
Licence
Funders
  • National Institutes of Health (GM105718, AG047270)
  • Ellison Medical Foundation
  • NIH (NS036251, DK45735)

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