Axonal transport deficits and neurodegenerative diseases

Stéphanie Millecamps; Jean-Pierre Julien

doi:10.1038/nrn3380

journal article Jan 30, 2013

Axonal transport deficits and neurodegenerative diseases

Stéphanie Millecamps

Jean-Pierre Julien

Nature Reviews Neuroscience Vol. 14 No. 3 pp. 161-176 · Springer Science and Business Media LLC

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References

179

[1]

Perlson, E., Maday, S., Fu, M. M., Moughamian, A. J. & Holzbaur, E. L. Retrograde axonal transport: pathways to cell death? Trends Neurosci. 33, 335–344 (2010). 10.1016/j.tins.2010.03.006

[2]

Roy, S. et al. Neurofilaments are transported rapidly but intermittently in axons: implications for slow axonal transport. J. Neurosci. 20, 6849–6861 (2000). 10.1523/jneurosci.20-18-06849.2000

[3]

Wang, L., Ho, C. L., Sun, D., Liem, R. K. & Brown, A. Rapid movement of axonal neurofilaments interrupted by prolonged pauses. Nature Cell Biol. 2, 137–141 (2000). References 2 and 3 show that the slow axonal transport rate of neurofilaments is the result of rapid movements and prolonged pauses. 10.1038/35004008

[4]

Maday, S., Wallace, K. E. & Holzbaur, E. L. Autophagosomes initiate distally and mature during transport toward the cell soma in primary neurons. J. Cell Biol. 196, 407–417 (2012). 10.1083/jcb.201106120

[5]

Millecamps, S., Gowing, G., Corti, O., Mallet, J. & Julien, J. P. Conditional NF-L transgene expression in mice for in vivo analysis of turnover and transport rate of neurofilaments. J. Neurosci. 27, 4947–4956 (2007). This study shows that the axonal transport rate of cytoskeleton components in vivo depends on the density of the stationary network in the axons. 10.1523/jneurosci.5299-06.2007

[6]

Perrot, R. & Julien, J. P. Real-time imaging reveals defects of fast axonal transport induced by disorganization of intermediate filaments. FASEB J. 23, 3213–3225 (2009). This study demonstrates that changes in the stoichiometry of intermediate filaments can provoke defects of fast axonal transport of organelles like mitochondria. 10.1096/fj.09-129585

[7]

Lasek, R. J., Garner, J. A. & Brady, S. T. Axonal transport of the cytoplasmic matrix. J. Cell Biol. 99, 212s–221s (1984). 10.1083/jcb.99.1.212s

[8]

Xia, C. H. et al. Abnormal neurofilament transport caused by targeted disruption of neuronal kinesin heavy chain KIF5A. J. Cell Biol. 161, 55–66 (2003). This study analyses the consequences of kinesin disruption in mice and provides evidence for a role of kinesin in neurofilament transport. 10.1083/jcb.200301026

[9]

Uchida, A., Alami, N. H. & Brown, A. Tight functional coupling of kinesin-1A and dynein motors in the bidirectional transport of neurofilaments. Mol. Biol. Cell 20, 4997–5006 (2009). 10.1091/mbc.e09-04-0304

[10]

Hirokawa, N., Niwa, S. & Tanaka, Y. Molecular motors in neurons: transport mechanisms and roles in brain function, development, and disease. Neuron 68, 610–638 (2010). 10.1016/j.neuron.2010.09.039

[11]

Hirokawa, N. & Noda, Y. Intracellular transport and kinesin superfamily proteins, KIFs: structure, function, and dynamics. Physiol. Rev. 88, 1089–1118 (2008). 10.1152/physrev.00023.2007

[12]

Reed, N. A. et al. Microtubule acetylation promotes kinesin-1 binding and transport. Curr. Biol. 16, 2166–2172 (2006). 10.1016/j.cub.2006.09.014

[13]

Verhey, K. J. et al. Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules. J. Cell Biol. 152, 959–970 (2001). 10.1083/jcb.152.5.959

[14]

Setou, M. et al. Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to dendrites. Nature 417, 83–87 (2002). 10.1038/nature743

[15]

Eschbach, J. & Dupuis, L. Cytoplasmic dynein in neurodegeneration. Pharmacol. Ther. 130, 348–363 (2011). 10.1016/j.pharmthera.2011.03.004

[16]

DYNACTIN

Trina A. Schroer

Annual Review of Cell and Developmental Biology 2004 10.1146/annurev.cellbio.20.012103.094623

[17]

Hammer, J. A. & Sellers, J. R. Walking to work: roles for class V myosins as cargo transporters. Nature Rev. Mol. Cell Biol. 13, 13–26 (2012). 10.1038/nrm3248

[18]

Huang, J. D. et al. Direct interaction of microtubule- and actin-based transport motors. Nature 397, 267–270 (1999). 10.1038/16722

[19]

Cao, T. T., Chang, W., Masters, S. E. & Mooseker, M. S. Myosin-Va binds to and mechanochemically couples microtubules to actin filaments. Mol. Biol. Cell 15, 151–161 (2004). 10.1091/mbc.e03-07-0504

[20]

Rao, M. V. et al. Myosin Va binding to neurofilaments is essential for correct myosin Va distribution and transport and neurofilament density. J. Cell Biol. 159, 279–290 (2002). 10.1083/jcb.200205062

[21]

Rao, M. V. et al. The myosin Va head domain binds to the neurofilament-L rod and modulates endoplasmic reticulum (ER) content and distribution within axons. PLoS ONE 6, e17087 (2011). 10.1371/journal.pone.0017087

[22]

Lalli, G., Gschmeissner, S. & Schiavo, G. Myosin Va and microtubule-based motors are required for fast axonal retrograde transport of tetanus toxin in motor neurons. J. Cell Sci. 116, 4639–4650 (2003). 10.1242/jcs.00727

[23]

Ali, M. Y. et al. Myosin Va maneuvers through actin intersections and diffuses along microtubules. Proc. Natl Acad. Sci. USA 104, 4332–4336 (2007). 10.1073/pnas.0611471104

[24]

Lee, K. D. & Hollenbeck, P. J. Phosphorylation of kinesin in vivo correlates with organelle association and neurite outgrowth. J. Biol. Chem. 270, 5600–5605 (1995). 10.1074/jbc.270.10.5600

[25]

Morfini, G., Szebenyi, G., Elluru, R., Ratner, N. & Brady, S. T. Glycogen synthase kinase 3 phosphorylates kinesin light chains and negatively regulates kinesin-based motility. EMBO J. 21, 281–293 (2002). This study documents the mechanism of kinesin regulation by GSK3. 10.1093/emboj/21.3.281

[26]

Cross, D. A. et al. Insulin activates protein kinase B, inhibits glycogen synthase kinase-3 and activates glycogen synthase by rapamycin-insensitive pathways in skeletal muscle and adipose tissue. FEBS Lett. 406, 211–215 (1997). 10.1016/s0014-5793(97)00240-8

[27]

Cook, D. et al. Wingless inactivates glycogen synthase kinase-3 via an intracellular signalling pathway which involves a protein kinase C. EMBO J. 15, 4526–4536 (1996). 10.1002/j.1460-2075.1996.tb00830.x

[28]

Ivaska, J. et al. Integrin α2β1 promotes activation of protein phosphatase 2A and dephosphorylation of Akt and glycogen synthase kinase 3β. Mol. Cell. Biol. 22, 1352–1359 (2002). 10.1128/mcb.22.5.1352-1359.2002

[29]

Ratner, N., Bloom, G. S. & Brady, S. T. A role for cyclin-dependent kinase(s) in the modulation of fast anterograde axonal transport: effects defined by olomoucine and the APC tumor suppressor protein. J. Neurosci. 18, 7717–7726 (1998). 10.1523/jneurosci.18-19-07717.1998

[30]

Morfini, G. et al. A novel CDK5-dependent pathway for regulating GSK3 activity and kinesin-driven motility in neurons. EMBO J. 23, 2235–2245 (2004). 10.1038/sj.emboj.7600237

[31]

Ackerley, S. et al. Neurofilament heavy chain side arm phosphorylation regulates axonal transport of neurofilaments. J. Cell Biol. 161, 489–495 (2003). 10.1083/jcb.200303138

[32]

Shea, T. B. et al. Cdk5 regulates axonal transport and phosphorylation of neurofilaments in cultured neurons. J. Cell Sci. 117, 933–941 (2004). 10.1242/jcs.00785

[33]

Jung, C. et al. The high and middle molecular weight neurofilament subunits regulate the association of neurofilaments with kinesin: inhibition by phosphorylation of the high molecular weight subunit. Brain Res. Mol. Brain Res. 141, 151–155 (2005). 10.1016/j.molbrainres.2005.08.009

[34]

Dixit, R., Ross, J. L., Goldman, Y. E. & Holzbaur, E. L. Differential regulation of dynein and kinesin motor proteins by tau. Science 319, 1086–1089 (2008). This report demonstrates that tau detaches kinesin from microtubules and reverses the direction of dynein transport. 10.1126/science.1152993

[35]

Vershinin, M., Carter, B. C., Razafsky, D. S., King, S. J. & Gross, S. P. Multiple-motor based transport and its regulation by Tau. Proc. Natl Acad. Sci. USA 104, 87–92 (2007). 10.1073/pnas.0607919104

[36]

McVicker, D. P., Chrin, L. R. & Berger, C. L. The nucleotide-binding state of microtubules modulates kinesin processivity and the ability of Tau to inhibit kinesin-mediated transport. J. Biol. Chem. 286, 42873–42880 (2011). 10.1074/jbc.m111.292987

[37]

Yuan, A., Kumar, A., Peterhoff, C., Duff, K. & Nixon, R. A. Axonal transport rates in vivo are unaffected by tau deletion or overexpression in mice. J. Neurosci. 28, 1682–1687 (2008). 10.1523/jneurosci.5242-07.2008

[38]

Stable Kinesin and Dynein Assemblies Drive the Axonal Transport of Mammalian Prion Protein Vesicles

Sandra E. Encalada, Lukasz Szpankowski, Chun-hong Xia et al.

Cell 2011 10.1016/j.cell.2011.01.021

[39]

Hardy, J. A hundred years of Alzheimer's disease research. Neuron 52, 3–13 (2006). 10.1016/j.neuron.2006.09.016

[40]

Stokin, G. B. et al. Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease. Science 307, 1282–1288 (2005). 10.1126/science.1105681

[41]

Salehi, A. et al. Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron 51, 29–42 (2006). 10.1016/j.neuron.2006.05.022

[42]

Pigino, G. et al. Alzheimer's presenilin 1 mutations impair kinesin-based axonal transport. J. Neurosci. 23, 4499–4508 (2003). 10.1523/jneurosci.23-11-04499.2003

[43]

Lazarov, O. et al. Impairments in fast axonal transport and motor neuron deficits in transgenic mice expressing familial Alzheimer's disease-linked mutant presenilin 1. J. Neurosci. 27, 7011–7020 (2007). 10.1523/jneurosci.4272-06.2007

[44]

Ishihara, T. et al. Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform. Neuron 24, 751–762 (1999). 10.1016/s0896-6273(00)81127-7

[45]

Zhang, B. et al. Retarded axonal transport of R406W mutant tau in transgenic mice with a neurodegenerative tauopathy. J. Neurosci. 24, 4657–4667 (2004). References 40–45 support a role for early axonal transport deficits in the pathophysiology observed in rodent models of Alzheimer's disease. 10.1523/jneurosci.0797-04.2004

[46]

Kamal, A., Almenar-Queralt, A., LeBlanc, J. F., Roberts, E. A. & Goldstein, L. S. Kinesin-mediated axonal transport of a membrane compartment containing β-secretase and presenilin-1 requires APP. Nature 414, 643–648 (2001). 10.1038/414643a

[47]

Lazarov, O. et al. Axonal transport, amyloid precursor protein, kinesin-1, and the processing apparatus: revisited. J. Neurosci. 25, 2386–2395 (2005). 10.1523/jneurosci.3089-04.2005

[48]

Goldsbury, C. et al. Inhibition of APP trafficking by tau protein does not increase the generation of amyloid-β peptides. Traffic 7, 873–888 (2006). 10.1111/j.1600-0854.2006.00434.x

[49]

Hiruma, H., Katakura, T., Takahashi, S., Ichikawa, T. & Kawakami, T. Glutamate and amyloid β-protein rapidly inhibit fast axonal transport in cultured rat hippocampal neurons by different mechanisms. J. Neurosci. 23, 8967–8977 (2003). 10.1523/jneurosci.23-26-08967.2003

[50]

Rui, Y., Tiwari, P., Xie, Z. & Zheng, J. Q. Acute impairment of mitochondrial trafficking by β-amyloid peptides in hippocampal neurons. J. Neurosci. 26, 10480–10487 (2006). 10.1523/jneurosci.3231-06.2006

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Published: Jan 30, 2013
Vol/Issue: 14(3)
Pages: 161-176
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Stéphanie Millecamps, Jean-Pierre Julien (2013). Axonal transport deficits and neurodegenerative diseases. Nature Reviews Neuroscience, 14(3), 161-176. https://doi.org/10.1038/nrn3380

Axonal transport deficits and neurodegenerative diseases

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