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Tau phosphorylation and PAD exposure in regulation of axonal growth

Morris, S. L., Brady, S. T.·2023·Frontiers in Cell and Developmental Biology
DOI 10.3389/fcell.2022.1023418PMC PMC9893789
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Abstract

Introduction: Tau is a microtubule associated phosphoprotein found principally in neurons. Prevailing dogma continues to define microtubule stabilization as the major function of tau in vivo, despite several lines of evidence suggesting this is not the case. Most importantly, tau null mice have deficits in axonal outgrowth and neuronal migration while still possessing an extensive microtubule network. Instead, mounting evidence suggests that tau may have a major function in the regulation of fast axonal transport (FAT) through activation of neuronal signaling pathways. Previous studies identified a phosphatase activating domain (PAD) at the tau N-terminal that is normally sequestered, but is constitutively exposed in tauopathies. When exposed, the PAD activates a signaling cascade involving PP1 and GSK3β which affects cellular functions including release of cargo from kinesin. Furthermore, we discovered that PAD exposure can be regulated by a single phosphorylation at T205. Exposure of the PAD is an early event in multiple tauopathies and a major contributing factor to neurodegeneration associated with tau hyperphosphorylation. However, effects of tau PAD exposure on anterograde FAT raised the interesting possibility that this pathway may be a mechanism for physiological regulation of cargo delivery through site-specific phosphorylation of tau and transient activation of PP1 and GSK3β. Significantly, there is already evidence of local control of PP1 and GSK3β at sites which require cargo delivery. Methods: To investigate this hypothesis, first we evaluated cellular localization of tau PAD exposure, pT205 tau phosphorylation, and active GSK3β in primary hippocampal neurons during development. Second, we analyzed the axonal outgrowth of tau knockout neurons following transfection with full length hTau40-WT, hTau40-ΔPAD, or hTau40-T205A. Results and Discussion: The results presented here suggest that transient activation of a PP1-GSK3β signaling pathway through locally regulated PAD exposure is a mechanism for cargo delivery, and thereby important for neurite outgrowth of developing neurons.

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FIGURE 1 Schematics of DNA constructs used for transfection and representative outgrowth images. (A) Schematics of full length hTau40 DNA used for transfection of tau KO hippocampal. Neurons were transfected 16–18 h after plating and maintained in culture for a further 72 h. (B) 1) Representative image before neurite measurement. Blue: DAPI, White: β3-tubulin). All living neurons, judged by nucleus and tubulin integrity, fully contained in the image were identified and numbered prior to neurite measurement. 2) Representative image of tubulin immunocytochemistry after neurite measurement with the NeuronJ plugin. All neurites and branches are measured before being characterized as primary (magenta, *), secondary (yellow, ■), or tertiary (red, ▲).
FIGURE 1 Schematics of DNA constructs used for transfection and representative outgrowth images. (A) Schematics of full length hTau40 DNA used for transfection of tau KO hippocampal. Neurons were transfected 16–18 h after plating and maintained in culture for a further 72 h. (B) 1) Representative image before neurite measurement. Blue: DAPI, White: β3-tubulin). All living neurons, judged by nucleus and tubulin integrity, fully contained in the image were identified and numbered prior to neurite measurement. 2) Representative image of tubulin immunocytochemistry after neurite measurement with the NeuronJ plugin. All neurites and branches are measured before being characterized as primary (magenta, *), secondary (yellow, ■), or tertiary (red, ▲).CC BY · PubMed Central
FIGURE 2 Active dp-Ser9-GSK3β, PAD exposure, and pT205 tau are localized in growth cones. WT hippocampal neurons cultured for two DIV (A–C) or 10 DIV (D–E) were immunostained for inactive phospho-Ser9-GS3β (green) and active dephospho-Ser9-GSK3β (red) (A, D) or TNT1 (red) (B, C, E), total tau (white) (B) or pT205 tau (green) (C, E). All neurons were also stained with phalloidin to visualize actin (magenta). (A,D) Active dpGSK3β is enriched in the central region of the growth cone (arrowheads) whereas inactive pGSK3β is evenly distributed along the growing neurite and throughout the growth cone (arrows). (C, E) At both early and late developmental timepoints, TNT1 and pT205 tau immunoreactivity are visible at the end of growing neurites and the central region of growth cones. Scale bars: 5 μm (2 DIV); 10 μm (10 DIV).
FIGURE 2 Active dp-Ser9-GSK3β, PAD exposure, and pT205 tau are localized in growth cones. WT hippocampal neurons cultured for two DIV (A–C) or 10 DIV (D–E) were immunostained for inactive phospho-Ser9-GS3β (green) and active dephospho-Ser9-GSK3β (red) (A, D) or TNT1 (red) (B, C, E), total tau (white) (B) or pT205 tau (green) (C, E). All neurons were also stained with phalloidin to visualize actin (magenta). (A,D) Active dpGSK3β is enriched in the central region of the growth cone (arrowheads) whereas inactive pGSK3β is evenly distributed along the growing neurite and throughout the growth cone (arrows). (C, E) At both early and late developmental timepoints, TNT1 and pT205 tau immunoreactivity are visible at the end of growing neurites and the central region of growth cones. Scale bars: 5 μm (2 DIV); 10 μm (10 DIV).CC BY · PubMed Central
FIGURE 3 PAD exposure and pT205 tau localization changes and becomes progressively more restricted through neuronal development. WT hippocampal neurons cultured for 2 (A, B), 7 (C), or 10 DIV (D) were stained for TNT1 (red) and/or pT205 tau (green), actin (phalloidin; magenta), and MAP2 (white). At 2DIV TNT1 immunoreactivity is visible within the cell body and along the longest neurite. There is less PAD exposure in minor processes and branches (A, arrows). Similarly, pT205 tau immunoreactivity is equally distributed along the longest neurite and within the cell body but is not enriched in minor processes (B, arrows). At 7DIV, TNT1 immunoreactivity is observed in the cell body and at the end of the longest neurite (C, arrowhead) as well as in some minor processes (C, arrows). By 10DIV, PAD exposure and pT205 tau are localized to potential synaptic sites. pT205 tau and PAD exposure are localized are restricted subdomains along the axon at axonal-axonal or axonal-cell body crossing points (D, arrowheads). Neither pT205 nor TNT1 immunoreactivity is enriched in MAP2-positive dendrites (D, arrows). Scale bars: 10 μm (A, B, D) or 20 μm (C).
FIGURE 3 PAD exposure and pT205 tau localization changes and becomes progressively more restricted through neuronal development. WT hippocampal neurons cultured for 2 (A, B), 7 (C), or 10 DIV (D) were stained for TNT1 (red) and/or pT205 tau (green), actin (phalloidin; magenta), and MAP2 (white). At 2DIV TNT1 immunoreactivity is visible within the cell body and along the longest neurite. There is less PAD exposure in minor processes and branches (A, arrows). Similarly, pT205 tau immunoreactivity is equally distributed along the longest neurite and within the cell body but is not enriched in minor processes (B, arrows). At 7DIV, TNT1 immunoreactivity is observed in the cell body and at the end of the longest neurite (C, arrowhead) as well as in some minor processes (C, arrows). By 10DIV, PAD exposure and pT205 tau are localized to potential synaptic sites. pT205 tau and PAD exposure are localized are restricted subdomains along the axon at axonal-axonal or axonal-cell body crossing points (D, arrowheads). Neither pT205 nor TNT1 immunoreactivity is enriched in MAP2-positive dendrites (D, arrows). Scale bars: 10 μm (A, B, D) or 20 μm (C).CC BY · PubMed Central
FIGURE 4 Active phospho-Ser9-GSK3β is localized at specific locations in developing neurons. WT hippocampal neurons cultured for 2 (A) or 10 DIV (B) were stained for inactive phosphor-Ser9-GS3β (green), active dephospho-Ser9-GSK3β (red), and actin (phalloidin). In early development punctate staining of inactive pGS3β is visible along the length of the growing neurites whereas active dp-GSK3β has more limited localization (A). In later development, active dpGSK3β is localized at specific subdomains of the axon at points of axonal crossing (B, arrowheads), as well as in the cell body. Scale bars: 10 μm.
FIGURE 4 Active phospho-Ser9-GSK3β is localized at specific locations in developing neurons. WT hippocampal neurons cultured for 2 (A) or 10 DIV (B) were stained for inactive phosphor-Ser9-GS3β (green), active dephospho-Ser9-GSK3β (red), and actin (phalloidin). In early development punctate staining of inactive pGS3β is visible along the length of the growing neurites whereas active dp-GSK3β has more limited localization (A). In later development, active dpGSK3β is localized at specific subdomains of the axon at points of axonal crossing (B, arrowheads), as well as in the cell body. Scale bars: 10 μm.CC BY · PubMed Central
FIGURE 5 Tau KO hippocampal neurons have impaired neurite outgrowth and branching compared to WT neurons. Primary hippocampal neurons from WT and tau KO mice were cultured on poly-l-lysine + laminin for 24, 48, 72, or 96 h followed by staining for β3-tubulin. (A) WT hippocampal neurons (i–v) progress through the known stages of neurite outgrowth (Fletcher and Banker, 1989). By contrast, Tau KO hippocampal neurons (v-viii) have less neurite outgrowth and complexity than WT neurons at all timepoints. Blue: DAPI, White: β3-tubulin. Scale bars: 50 μm (B) Primary hippocampal neurons from tau KO mice have significantly shorter total neurite outgrowth length compared to WT neurons starting from 24 h of culture and continuing to 96 h of culture. (C) The longest primary neurite (axon) was significantly shorter for tau KO hippocampal neurons compared to WT. (D) The length of other primary neurites (dendrites) was significantly longer for WT hippocampal neurons compared to tau KO neurons at all timepoints. (E) The number of primary neurites remained consistent from 24h–96 h of culture for both WT and tau KO hippocampal neurons and was significantly for WT neurons at all timepoints. (F) WT hippocampal neurons have an overall higher number of axonal and dendritic branches than tau KO neurons from 24 to 96 h in culture. (G) Primary hippocampal neurons from tau KO mice have significantly shorter secondary and tertiary neurite lengths than WT neurons at the equivalent timepoint in culture. (H) WT hippocampal neurons have a significantly higher number of axonal branches than tau KO neurons. N = 96–119 individual neurons analyzed (see Supplementary Tables 2 & 3). ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05.
FIGURE 5 Tau KO hippocampal neurons have impaired neurite outgrowth and branching compared to WT neurons. Primary hippocampal neurons from WT and tau KO mice were cultured on poly-l-lysine + laminin for 24, 48, 72, or 96 h followed by staining for β3-tubulin. (A) WT hippocampal neurons (i–v) progress through the known stages of neurite outgrowth (Fletcher and Banker, 1989). By contrast, Tau KO hippocampal neurons (v-viii) have less neurite outgrowth and complexity than WT neurons at all timepoints. Blue: DAPI, White: β3-tubulin. Scale bars: 50 μm (B) Primary hippocampal neurons from tau KO mice have significantly shorter total neurite outgrowth length compared to WT neurons starting from 24 h of culture and continuing to 96 h of culture. (C) The longest primary neurite (axon) was significantly shorter for tau KO hippocampal neurons compared to WT. (D) The length of other primary neurites (dendrites) was significantly longer for WT hippocampal neurons compared to tau KO neurons at all timepoints. (E) The number of primary neurites remained consistent from 24h–96 h of culture for both WT and tau KO hippocampal neurons and was significantly for WT neurons at all timepoints. (F) WT hippocampal neurons have an overall higher number of axonal and dendritic branches than tau KO neurons from 24 to 96 h in culture. (G) Primary hippocampal neurons from tau KO mice have significantly shorter secondary and tertiary neurite lengths than WT neurons at the equivalent timepoint in culture. (H) WT hippocampal neurons have a significantly higher number of axonal branches than tau KO neurons. N = 96–119 individual neurons analyzed (see Supplementary Tables 2 & 3). ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05.CC BY · PubMed Central
FIGURE 6 Transfection with hTau40-WT, but not with hTau40-ΔPAD and hTau40-T205A, improves neurite outgrowth of tau KO hippocampal neurons. Primary hippocampal neurons from tau KO mice cultured on poly-l-lysine + laminin were transfected 16–18 h after plating and cultured for a further 72 h before fixation and staining for β3-tubulin. (A) Tau KO hippocampal neurons have limited neurite outgrowth after 96 h 1) but outgrowth is improved after transfection with hTau40-WT 2). By contrast, transfection of Tau KO hippocampal neurons with hTau40-ΔPAD 3) or hTau40-T205A (iv) does not improve neurite outgrowth compared to untransfected tau KO hippocampal neurons. Blue: DAPI, White: β3-tubulin. Scale bars: 50 μm. (B) The total length of all neurites is increased by transfection of hTau40-WT (p = 0.0014) but not hTau40-ΔPAD (p = 0.963) or hTau40-T205A (p = 0.81). (C) The number of primary neurites for tau KO neurons was slightly increased by transfection of hTau40-WT but did not reach significance (p = 0.1937). hTau40-ΔPAD (p > 0.999) or hTau40-T205A (p > 0.999) transfection did not increase the number of primary neurites. (D) Impaired axonal outgrowth was significantly improved by transfection of hTau40-WT (p = 0.0005). By contrast, transfection of hTau40-ΔPAD did not increase axonal outgrowth (p = 0.944). After transfection of hTau40-T205A tau KO actually showed less axonal outgrowth than untransfected neurons (p = 0.0242). (E) Dendritic outgrowth was also increased by transfection with hTau40-WT (p = 0.0005). Transfection of hTau40-ΔPAD (p > 0.999) or hTau40-T205A (p > 0.999) did not increase dendritic outgrowth. (F) The total number of branches of tau KO hippocampal neurons transfected with hTau40-WT (p > 0.999), hTau40-ΔPAD (p = 0.424) or hTau40-T205A (p = 0.986) was not increased. (G) The number of axonal branches after transfection with hTau40-WT (p > 0.999), hTau40-ΔPAD (p = 0.093) or hTau40-T205A (p = 0.430) was not increased. (H) The total length of tau KO neuron axonal and dendritic branches was not increased by transfection with hTau40-WT (p = 0.999), hTau40-ΔPAD (p = 0.698) or hTau40-T205A (p = 0.698). All data was collected after 96 h in culture. N = 101–115 individual neurons analyzed (see Supplementary Tables S4, 5). ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05.
FIGURE 6 Transfection with hTau40-WT, but not with hTau40-ΔPAD and hTau40-T205A, improves neurite outgrowth of tau KO hippocampal neurons. Primary hippocampal neurons from tau KO mice cultured on poly-l-lysine + laminin were transfected 16–18 h after plating and cultured for a further 72 h before fixation and staining for β3-tubulin. (A) Tau KO hippocampal neurons have limited neurite outgrowth after 96 h 1) but outgrowth is improved after transfection with hTau40-WT 2). By contrast, transfection of Tau KO hippocampal neurons with hTau40-ΔPAD 3) or hTau40-T205A (iv) does not improve neurite outgrowth compared to untransfected tau KO hippocampal neurons. Blue: DAPI, White: β3-tubulin. Scale bars: 50 μm. (B) The total length of all neurites is increased by transfection of hTau40-WT (p = 0.0014) but not hTau40-ΔPAD (p = 0.963) or hTau40-T205A (p = 0.81). (C) The number of primary neurites for tau KO neurons was slightly increased by transfection of hTau40-WT but did not reach significance (p = 0.1937). hTau40-ΔPAD (p > 0.999) or hTau40-T205A (p > 0.999) transfection did not increase the number of primary neurites. (D) Impaired axonal outgrowth was significantly improved by transfection of hTau40-WT (p = 0.0005). By contrast, transfection of hTau40-ΔPAD did not increase axonal outgrowth (p = 0.944). After transfection of hTau40-T205A tau KO actually showed less axonal outgrowth than untransfected neurons (p = 0.0242). (E) Dendritic outgrowth was also increased by transfection with hTau40-WT (p = 0.0005). Transfection of hTau40-ΔPAD (p > 0.999) or hTau40-T205A (p > 0.999) did not increase dendritic outgrowth. (F) The total number of branches of tau KO hippocampal neurons transfected with hTau40-WT (p > 0.999), hTau40-ΔPAD (p = 0.424) or hTau40-T205A (p = 0.986) was not increased. (G) The number of axonal branches after transfection with hTau40-WT (p > 0.999), hTau40-ΔPAD (p = 0.093) or hTau40-T205A (p = 0.430) was not increased. (H) The total length of tau KO neuron axonal and dendritic branches was not increased by transfection with hTau40-WT (p = 0.999), hTau40-ΔPAD (p = 0.698) or hTau40-T205A (p = 0.698). All data was collected after 96 h in culture. N = 101–115 individual neurons analyzed (see Supplementary Tables S4, 5). ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05.CC BY · PubMed Central

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Cites

Research works printed but not linked: 62

  1. Ahmari, 2000, Assembly of presynaptic active zones from cytoplasmic transport packets, Nat. Neurosci., 3, 445, 10.1038/74814 · DOI
  2. Ahmari, 2002, Knowing a nascent synapse when you see it, Neuron, 34, 333, 10.1016/s0896-6273(02)00685-2 · DOI
  3. Bartlett, 1984, An electron microscopic study of the development of axons and dendrites by hippocampal neurons in culture. II. Synaptic relationships, J. Neurosci. Off. J. Soc. Neurosci., 4, 1954, 10.1523/JNEUROSCI.04-08-01954.1984 · DOI · Paper page
  4. Bibow, 2011, Structural impact of proline-directed pseudophosphorylation at AT8, AT100, and PHF1 epitopes on 441-residue tau, J. Am. Chem. Soc., 133, 15842, 10.1021/ja205836j · DOI
  5. Bolte, 2006, A guided tour into subcellular colocalization analysis in light microscopy, J. Microsc., 224, 213, 10.1111/j.1365-2818.2006.01706.x · DOI
  6. Bury, 2011, Coordinated trafficking of synaptic vesicle and active zone proteins prior to synapse formation, Neural Dev., 6, 24, 10.1186/1749-8104-6-24 · DOI
  7. Caceres, 1990, Inhibition of neurite polarity by tau antisense oligonucleotides in primary cerebellar neurons, Nature, 343, 461, 10.1038/343461a0 · DOI · Paper page
  8. Caceres, 1991, The effect of tau antisense oligonucleotides on neurite formation of cultured cerebellar macroneurons, J. Neurosci. Off. J. Soc. Neurosci., 11, 1515, 10.1523/JNEUROSCI.11-06-01515.1991 · DOI · Paper page
  9. Combs, 2016, Pathological conformations involving the amino terminus of tau occur early in Alzheimer’s disease and are differentially detected by monoclonal antibodies, Neurobiol. Dis., 94, 18, 10.1016/j.nbd.2016.05.016 · DOI
  10. Combs, 2017, Exposure of the amino terminus of tau is a pathological event in multiple tauopathies, Am. J. Pathol., 187, 1222, 10.1016/j.ajpath.2017.01.019 · DOI
  11. Cox, 2016, Analysis of isoform-specific tau aggregates suggests a common toxic mechanism involving similar pathological conformations and axonal transport inhibition, Neurobiol. Aging, 47, 113, 10.1016/j.neurobiolaging.2016.07.015 · DOI
  12. Craig, 1995, Preferential addition of newly synthesized membrane protein at axonal growth cones, Nature, 375, 592, 10.1038/375592a0 · DOI
  13. Dawson, 2001, Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice, J. Cell Sci., 114, 1179, 10.1242/jcs.114.6.1179 · DOI · Paper page
  14. de Waegh, 1992, Local modulation of neurofilament phosphorylation, axonal caliber, and slow axonal transport by myelinating Schwann cells, Cell, 68, 451, 10.1016/0092-8674(92)90183-D · DOI
  15. DeBoer, 2008, Conventional kinesin holoenzymes are composed of heavy and light chain homodimers, Biochemistry, 47, 4535, 10.1021/bi702445j · DOI
  16. Devaux, 2012, Specific serine-proline phosphorylation and glycogen synthase kinase 3β-directed subcellular targeting of stathmin 3/Sclip in neurons, J. Biol. Chem., 287, 22341, 10.1074/jbc.M112.344044 · DOI
  17. DiTella, 1996, MAP-1B/TAU functional redundancy during laminin-enhanced axonal growth, J. Cell Sci., 109, 467, 10.1242/jcs.109.2.467 · DOI
  18. Dotti, 1988, The establishment of polarity by hippocampal neurons in culture, J. Neurosci. Off. J. Soc. Neurosci., 8, 1454, 10.1523/JNEUROSCI.08-04-01454.1988 · DOI · Paper page
  19. Dubourg, 2011, Clinical and molecular characterization of 17q21.31 microdeletion syndrome in 14 French patients with mental retardation, Eur. J. Med. Genet., 54, 144, 10.1016/j.ejmg.2010.11.003 · DOI
  20. Fiock, 2020, Increased tau expression correlates with neuronal maturation in the developing human cerebral cortex, eNeuro, 7, ENEURO.0058, 10.1523/ENEURO.0058-20.2020 · DOI
  21. Fletcher, 1989, The establishment of polarity by hippocampal neurons: The relationship between the stage of a cell’s development in situ and its subsequent development in culture, Dev. Biol., 136, 446, 10.1016/0012-1606(89)90269-8 · DOI
  22. Futerman, 1996, The economics of neurite outgrowth — The addition of new membrane to growing axons, Trends Neurosci., 19, 144, 10.1016/S0166-2236(96)80025-7 · DOI
  23. Grabinski, 2016, Novel non-phosphorylated serine 9/21 gsk3β/α antibodies: Expanding the tools for studying GSK3 regulation, Front. Mol. Neurosci., 9, 123, 10.3389/fnmol.2016.00123 · DOI
  24. Harada, 1994, Altered microtubule organization in small-calibre axons of mice lacking tau protein, Nature, 369, 488, 10.1038/369488a0 · DOI · Paper page
  25. Hsieh, 1994, Regional modulation of neurofilament organization by myelination in normal axons, J. Neurosci. Off. J. Soc. Neurosci., 14, 6392, 10.1523/JNEUROSCI.14-11-06392.1994 · DOI
  26. Ikegami, 2000, Muscle weakness, hyperactivity, and impairment in fear conditioning in tau-deficient mice, Neurosci. Lett., 279, 129, 10.1016/S0304-3940(99)00964-7 · DOI
  27. Iworima, 2016, Kif5 regulates mitochondrial movement, morphology, function and neuronal survival, Mol. Cell. Neurosci., 72, 22, 10.1016/j.mcn.2015.12.014 · DOI
  28. Jacobson, 2006, A change in the selective translocation of the kinesin-1 motor domain marks the initial specification of the axon, Neuron, 49, 797, 10.1016/j.neuron.2006.02.005 · DOI
  29. Jeganathan, 2008, Proline-directed pseudo-phosphorylation at AT8 and PHF1 epitopes induces a compaction of the paperclip folding of tau and generates a pathological (MC-1) conformation, J. Biol. Chem., 283, 32066, 10.1074/jbc.M805300200 · DOI · Paper page
  30. Kanaan, 2016, Characterization of early pathological tau conformations and phosphorylation in chronic traumatic encephalopathy, J. Neuropathol. Exp. Neurol., 75, 19, 10.1093/jnen/nlv001 · DOI
  31. Kanaan, 2011, Pathogenic forms of tau inhibit kinesin-dependent axonal transport through a mechanism involving activation of axonal phosphotransferases, J. Neurosci. Off. J. Soc. Neurosci., 31, 9858, 10.1523/JNEUROSCI.0560-11.2011 · DOI
  32. Kanaan, 2012, Phosphorylation in the amino terminus of tau prevents inhibition of anterograde axonal transport, Neurobiol. Aging, 33, e15, 10.1016/j.neurobiolaging.2011.06.006 · DOI · Paper page
  33. Kanai, 2004, Kinesin transports RNA: Isolation and characterization of an RNA-transporting granule, Neuron, 43, 513, 10.1016/j.neuron.2004.07.022 · DOI
  34. Karasmanis, 2018, Polarity of neuronal membrane traffic requires sorting of kinesin motor cargo during entry into dendrites by a microtubule-associated septin, Dev. Cell, 46, 204, 10.1016/j.devcel.2018.06.013 · DOI
  35. Karle, 2012, Axonal transport deficit in a KIF5A(-/-) mouse model, Neurogenetics, 13, 169, 10.1007/s10048-012-0324-y · DOI
  36. LaPointe, 2009, The amino terminus of tau inhibits kinesin-dependent axonal transport: Implications for filament toxicity, J. Neurosci. Res., 87, 440, 10.1002/jnr.21850 · DOI
  37. Li, 2004, A syntaxin 1, galphao, and N-type calcium channel complex at a presynaptic nerve terminal: Analysis by quantitative immunocolocalization, J. Neurosci., 24, 4070, 10.1523/jneurosci.0346-04.2004 · DOI
  38. Liu, 2013, Profiling murine tau with 0N, 1N and 2N isoform-specific antibodies in brain and peripheral organs reveals distinct subcellular localization, with the 1N isoform being enriched in the nucleus, PLOS ONE, 8, e84849, 10.1371/journal.pone.0084849 · DOI
  39. Liu, 2005, Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation, Eur. J. Neurosci., 22, 1942, 10.1111/j.1460-9568.2005.04391.x · DOI · Paper page
  40. Liu, 2019, Loss of tau and Fyn reduces compensatory effects of MAP2 for tau and reveals a Fyn-independent effect of tau on calcium, J. Neurosci. Res. Jnr., 24517, 1393, 10.1002/jnr.24517 · DOI
  41. Martenson, 1993, Fast axonal transport is required for growth cone advance, Nature, 366, 66, 10.1038/366066a0 · DOI
  42. Martini, 2001, The effect of myelinating Schwann cells on axons, Muscle Nerve, 24, 456, 10.1002/mus.1027 · DOI
  43. Morfini, 2007, Tau binding to microtubules does not directly affect microtubule-based vesicle motility, J. Neurosci. Res., 85, 2620, 10.1002/jnr.21154 · DOI
  44. Morfini, 2004, A novel CDK5-dependent pathway for regulating GSK3 activity and kinesin-driven motility in neurons, EMBO J., 23, 2235, 10.1038/sj.emboj.7600237 · DOI
  45. Morfini, 2002, Glycogen synthase kinase 3 phosphorylates kinesin light chains and negatively regulates kinesin-based motility, EMBO J., 21, 281, 10.1093/emboj/21.3.281 · DOI
  46. Morris, 2021, Phosphorylation of tau at specific sites regulates axonal transport and neurite outgrowth
  47. Morris, 2021, Lack of neurosteroid selectivity at δ vs. γ2-containing GABAA receptors in dentate granule neurons, Front. Mol. Neurosci., 13, 6, 10.3389/fnmol.2020.00006 · DOI
  48. Nakata, 2003, Microtubules provide directional cues for polarized axonal transport through interaction with kinesin motor head, J. Cell Biol., 162, 1045, 10.1083/jcb.200302175 · DOI
  49. Pfenninger, 1993, Sites of plasmalemmal expansion in growth cones, Brain Res. Dev. Brain Res., 71, 181, 10.1016/0165-3806(93)90170-f · DOI
  50. Sapir, 2012, Tau’s role in the developing brain: Implications for intellectual disability, Hum. Mol. Genet., 21, 1681, 10.1093/hmg/ddr603 · DOI
  51. Sennvik, 2007, Tau-4R suppresses proliferation and promotes neuronal differentiation in the hippocampus of tau knockin/knockout mice, FASEB J., 21, 2149, 10.1096/fj.06-7735com · DOI · Paper page
  52. Setou, 2002, Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to dendrites, Nature, 417, 83, 10.1038/nature743 · DOI
  53. Shaw-Smith, 2006, Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability, Nat. Genet., 38, 1032, 10.1038/ng1858 · DOI
  54. Smith, 2018, The role of mitochondria in axon development and regeneration, Dev. Neurobiol., 78, 221, 10.1002/dneu.22546 · DOI
  55. Sontag, 2012, The protein phosphatase PP2A/bα binds to the microtubule-associated proteins tau and MAP2 at a motif also recognized by the kinase Fyn implications for tauopathies, J. Biol. Chem., 287, 14984, 10.1074/jbc.M111.338681 · DOI
  56. Szodorai, 2009, APP anterograde transport requires Rab3A GTPase activity for assembly of the transport vesicle, J. Neurosci., 29, 14534, 10.1523/JNEUROSCI.1546-09.2009 · DOI
  57. Takei, 2000, Defects in axonal elongation and neuronal migration in mice with disrupted tau and map1b genes, J. Cell Biol., 150, 989, 10.1083/jcb.150.5.989 · DOI
  58. Takuma, 2003, Isoforms changes of tau protein during development in various species, Dev. Brain Res., 142, 121, 10.1016/S0165-3806(03)00056-7 · DOI
  59. Trivedi, 2005, Glycogen synthase kinase-3beta phosphorylation of MAP1B at Ser1260 and Thr1265 is spatially restricted to growing axons, J. Cell Sci., 118, 993, 10.1242/jcs.01697 · DOI
  60. Wang, 2015, Rapid alteration of protein phosphorylation during postmortem: Implication in the study of protein phosphorylation, Sci. Rep., 5, 15709, 10.1038/srep15709 · DOI
  61. Washbourne, 2015, Synapse assembly and neurodevelopmental disorders, Neuropsychopharmacology, 40, 4, 10.1038/npp.2014.163 · DOI
  62. Weingarten, 1975, A protein factor essential for microtubule assembly, Proc. Natl. Acad. Sci., 72, 1858, 10.1073/pnas.72.5.1858 · DOI · Paper page

Cited by

See all 18

Metadata

Authors
Morris, S. L., & Brady, S. T.
Venue
Frontiers in Cell and Developmental Biology
Publisher
Frontiers Media SA
Published
2023-01-18
Volume
10
ISSN
2296-634X
DOI
10.3389/fcell.2022.1023418
PMC
PMC9893789
Cited by
18
References
3
Licence
creativecommons.org/licenses/by/4.0/ (vor)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.