The DOI matches its Crossref record; 68 of the 70 references it cites were found in a registry or an index.
Sorting mechanisms of Tau and MAP2 in neurons: Suppressed axonal transit of MAP2 and locally regulated microtubule binding
Open accessAbstract
Tau is abundant in the axon, whereas MAP2 is found in the cell body and dendrites. To understand their differential localization, we performed transfection studies on primary cultured neurons using tagged tau, MAP2, MAP2C, and their chimeric/deletion mutants. We found that MAP2 was prevented from entering the axon by its N-terminal projection domain and that microtubule binding of tau was stronger in the axon than in the cell body and dendrites, whereas that of MAP2/MAP2C was tighter in the cell body and dendrites than in the axon. These binding properties were determined by their microtubule-binding domains and were suggested to be regulated by phosphorylation, at least in the case of tau. Thus, the suppressed axonal transit of MAP2 and locally regulated microtubule binding may play important roles for their sorting in neurons.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Kanai et al. (6) also reported that the projection domain (PD) of MAP2, which exists only in MAP2A and B, prevents MAP2 from entering the axon, resulting in the somatodendritic localization of HMW MAP2”
From Active transport by cytoplasmic dynein sustains dendritic MAP2 localization in developing neurons (2026) · cites this paper as [6]
In the citing paper
“Tau is highly expressed in neurons in the mammalian brain, and normally localizes predominantly to axons as an important regulator of axonal transport [124–126].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [125]
Citations
Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961
A protein factor essential for microtubule assembly
Weingarten, M. D., Lockwood, A. H., Hwo, S. Y., & Kirschner, M. W. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.5.1858 · Cited by 3,089
Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product.
Evan, G. I., Lewis, G. K., Ramsay, G. M., & Bishop, J. M. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.12.3610 · Cited by 2,412
The distribution of tau in the mammalian central nervous system.
Binder, L. I., Frankfurter, A., & Rebhun, L. I. (1985) · The Journal of cell biology · doi:10.1083/jcb.101.4.1371 · Cited by 1,588
Goedert, M., Spillantini, M. G., Potier, M. C., Ulrich, J., & Crowther, R. A. (1989) · The EMBO Journal · doi:10.1002/j.1460-2075.1989.tb03390.x · Cited by 1,037
Cleveland, D. W., Hwo, S.-Y., & Kirschner, M. W. (1977) · Journal of Molecular Biology · doi:10.1016/0022-2836(77)90213-3 · Cited by 915
Physical and chemical properties of purified tau factor and the role of tau in microtubule assembly
Cleveland, D. W., Hwo, S. Y., & Kirschner, M. W. (1977) · Journal of Molecular Biology · doi:10.1016/0022-2836(77)90214-5 · Cited by 881
The Primary Structure and Heterogeneity of Tau Protein from Mouse Brain
Lee, G. S., Cowan, N. J., & Kirschner, M. W. (1988) · Science · doi:10.1126/science.3122323 · Cited by 680
Hirokawa, N. (1982) · The Journal of Cell Biology · doi:10.1083/jcb.94.1.129 · Cited by 667
Self-citationProjection domains of MAP2 and tau determine spacings between microtubules in dendrites and axons
Chen, J., Kanai, Y., Cowan, N. J., & Hirokawa, N. (1992) · Nature · doi:10.1038/360674a0 · Cited by 601
Self-citation
Cited by
Sorted by citations
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Kanai, Y., Dohmae, N., & Hirokawa, N. (2004) · Neuron · doi:10.1016/j.neuron.2004.07.022 · Cited by 1,109
Self-citationMolecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994
Molecular motors and mechanisms of directional transport in neurons
Hirokawa, N., & Takemura, R. (2005) · Nature reviews. Neuroscience · doi:10.1038/nrn1624 · Cited by 856
Self-citationCRMP-2 binds to tubulin heterodimers to promote microtubule assembly
Fukata, Y., Itoh, T. J., Kimura, T., Ménager, C., Nishimura, T., Shiromizu, T., Watanabe, H., Inagaki, N., Iwamatsu, A., Hotani, H., et al. (2002) · Nature Cell Biology · doi:10.1038/ncb825 · Cited by 761
The MAP1 family of microtubule-associated proteins.
Dehmelt (2004) · Genome biology · doi:10.1186/gb-2004-6-1-204 · Cited by 972
“[26], differential protein sorting [27], and dendrite-specific transport of MAP2 mRNA [28] are responsible for this spatial segregation of the two MAPs.”
Brandt, R., Léger, J. G., & Lee, G. S. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.131.5.1327 · Cited by 663
“Kanai and Hirokawa (1995) have suggested that the localization of tau to the axon is based on the microtubule binding properties of the carboxy terminal half of tau.”
Sánchez, C. (2000) · Progress in Neurobiology · doi:10.1016/s0301-0082(99)00046-5 · Cited by 521
The importance of tau phosphorylation for neurodegenerative diseases
Noble, W., Hanger, D. P., Miller, C. C. J., & Lovestone, S. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00083 · Cited by 475
Billingsley, M. L., & Kincaid, R. L. (1997) · Biochemical Journal · doi:10.1042/bj3230577 · Cited by 466
Trinczek, B., Ebneth, A., Mandelkow, E.-M., & Mandelkow, E. (1999) · Journal of Cell Science · doi:10.1242/jcs.112.14.2355 · Cited by 344
KIF5C, a Novel Neuronal Kinesin Enriched in Motor Neurons
Kanai, Y., Okada, Y., Tanaka, Y., Harada, A., Terada, S., & Hirokawa, N. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-17-06374.2000 · Cited by 334
“We constructed deleted fragments of the clones by the conventional 39 deletion method using Exonuclease III /mung bean nuclease (TaKaRa, Tokyo, Japan) to read the entire sequence (Kanai et al., 1992; Kanai and Hirokawa, 1995).”
MethodSelf-citationCompagnone, N. A., & Mellon, S. H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.8.4678 · Cited by 327
Andreadis, A. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.08.010 · Cited by 311
Dendritic Tau in Alzheimer’s Disease
Ittner, A., & Ittner, L. M. (2018) · Neuron · doi:10.1016/j.neuron.2018.06.003 · Cited by 278
Zempel, H., Luedtke, J., Kumar, Y., Biernat, J., Dawson, H., Mandelkow, E., & Mandelkow, E. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.207 · Cited by 283
“The basis for axonal Tau sorting in mature neurons is still not well understood, and several protein-based or mRNA-based mechanisms may work in parallel (Kanai and Hirokawa, 1995; Aronov et al , 2001; Nakata et al , 2011), including a retrograde barrier for Tau at the AIS (Li et al , 2011).”
Lost after translation: missorting of Tau protein and consequences for Alzheimer disease
Zempel, H., & Mandelkow�, E. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.08.004 · Cited by 284
Kempf, M., Clement, A. M., Faissner, A., Lee, G. S., & Brandt, R. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-18-05583.1996 · Cited by 248
“…with rhodamine-coupled phalloidin. that their localization is determined by mRNA localization (Garner et al., 1988; Litman et al., 1993), by locally differing protein turnover (Okabe and Hirokawa, 1989), or by locally regulated microtubule binding (Ferreira et al., 1993; Kanai and Hirokawa, 1995).”
Regulation of microtubule-associated proteins
Cassimeris, L., & Spittle, C. S. (2001) · International review of cytology · doi:10.1016/s0074-7696(01)10006-9 · Cited by 231
Fibroblast growth factor 14 is an intracellular modulator of voltage‐gated sodium channels
Lou, J.-Y., Laezza, F., Gerber, B. R., Xiao, M.-L., Yamada, K. A., Hartmann, H., Craig, A. M., Nerbonne, J., & Ornitz, D. M. (2005) · Journal of Physiology · doi:10.1113/jphysiol.2005.097220 · Cited by 216
“In these experiments, axons were identified as neuronal processes devoid of the microtubule-associated protein 2 (MAP2), a somato-dendritic marker (Kanai & Hirokawa, 1995).”
Brion, J., Tremp, G. L., & Octave, J. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65272-8 · Cited by 203
Quantification of Axonal Damage in Traumatic Brain Injury
Zemlan, F. P., Rosenberg, W. S., Luebbe, P., Campbell, T. A., Dean, G. E., Weiner, N. E., Cohen, J. A., Rudick, R. A., & Woo, D. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0720741.x · Cited by 187
Hirokawa, N., Funakoshi, T., Sato-Harada, R., & Kanai, Y. (1996) · The Journal of cell biology · doi:10.1083/jcb.132.4.667 · Cited by 179
“In the case of MAP2C, mRNA is confined to the cell body (Garner et al., 1988) and despite its transport of the protein into the axon (Kanai and Hirokawa , 1995), MAP2C is compartmentalized in cell bodies and dendrites in matured neurons (Tucker et al., 1988b).”
BackgroundResultInfluentialSelf-citationSaito, N., Okada, Y., Noda, Y., Kinoshita, Y., Kondo, S., & Hirokawa, N. (1997) · Neuron · doi:10.1016/s0896-6273(00)81243-x · Cited by 168
Self-citationMarszalek, J. R., Weiner, J. A., Farlow, S. J., Chun, J. J. M., & Goldstein, L. S. B. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.3.469 · Cited by 167
“There is some evidence that differences in protein stability between the axonal and dendritic processes can account for enrichment of protein within one of the processes (i.e., MAP2; Okabe and Hirokawa, 1989; Kanai and Hirokawa, 1995).”
BackgroundMore than a marker: potential pathogenic functions of MAP2
DeGiosio, R. A., Grubisha, M. J., MacDonald, M. L., McKinney, B. C., Camacho, C. J., & Sweet, R. A. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.974890 · Cited by 173
“An enhanced selectivity of the HMW forms for the dendritic compartment may be due to presence of the projection domain, which inhibits MAP2A/B access to axons (Kanai and Hirokawa, 1995), perhaps via interactions with axonal initial segment proteins such as AnkyrinG (Hedstrom et al.”
BackgroundChiasseu, M., Alarcón-Martínez, L., Belforte, N., Quintero, H., Dotigny, F., Destroismaisons, L., Velde, C. V., Panayi, F., Louis, C., & Polo, A. D. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0199-3 · Cited by 158
“Changes in tau phosphorylation might reduce its affinity for axonal microtubules and increase it for dendritic microtubules, as shown in cultured spinal cord neurons [113].”
Swimming against the Tide: Mobility of the Microtubule-Associated Protein Tau in Neurons
Konzack, S., Thies, E., Marx, A., Mandelkow, E., & Mandelkow�, E. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0927-07.2007 · Cited by 165
Differentiation of human ESCs to retinal ganglion cells using a CRISPR engineered reporter cell line
Sluch, V. M., Davis, C.-H. O., Jaskula-Ranga, V., Kerr, J. M., Krick, K., Martin, R., Berlinicke, C. A., Marsh‐Armstrong, N., Diamond, J. S., Mao, H., et al. (2015) · Scientific Reports · doi:10.1038/srep16595 · Cited by 156
Buchholz, S., & Zempel, H. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13784 · Cited by 154
Doublecortin-like kinase enhances dendritic remodelling and negatively regulates synapse maturation
Shin, E., Kashiwagi, Y., Kuriu, T., Iwasaki, H., Tanaka, T., Koizumi, H., Gleeson, J. G., & Okabe, S. (2013) · Nature Communications · doi:10.1038/ncomms2443 · Cited by 134
Tortosa, E., Adolfs, Y., Fukata, M., Pasterkamp, R. J., Kapitein, L. C., & Hoogenraad, C. C. (2017) · Neuron · doi:10.1016/j.neuron.2017.04.042 · Cited by 125
“…localizations in the neuron during the different stages of neuronal development (Conde and Ca´-ceres, 2009 (legend continued on next page) polarization of MAPs, like MAP2 and Tau (Garner et al., 1988; Hir-okawa et al., 1996; Kanai and Hirokawa, 1995; Li et al., 2011; Okabe and Hirokawa, 1989).”
Somatodendritic localization of phosphorylated tau in neonatal and adult rat cerebral cortex
Tashiro, K., Hasegawa, M., Ihara, Y., & Iwatsubo, T. (1997) · Neuroreport · doi:10.1097/00001756-199708180-00029 · Cited by 123
Acetylated Microtubules Are Preferentially Bundled Leading to Enhanced Kinesin-1 Motility
Balabanian, L., Berger, C. L., & Hendricks, A. G. (2017) · Biophysical Journal · doi:10.1016/j.bpj.2017.08.009 · Cited by 103
Tau Accumulation, Altered Phosphorylation, and Missorting Promote Neurodegeneration in Glaucoma
Chiasseu, M., Vargas, J. L. C., Destroismaisons, L., Velde, C. V., Leclerc, N. M., & Polo, A. D. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.3986-15.2016 · Cited by 105
Transport and diffusion of Tau protein in neurons
Scholz, T., & Mandelkow�, E. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1610-7 · Cited by 105
“How Tau is sorted into axons and/or depleted from the somatodendritic compartment is still not well understood, although several pathways have been discovered which may operate in parallel [8, 43, 51, 63, 110].”
BackgroundSato-Harada, R., Okabe, S., Umeyama, T., Kanai, Y., & Hirokawa, N. (1996) · Cell Structure and Function · doi:10.1247/csf.21.283 · Cited by 100
Self-citationZempel, H., & Mandelkow, E. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0064-1 · Cited by 100
“Proper axonal sorting of Tau depends on intact Tau-microtubule interactions [34].”
Tau's role in the developing brain: implications for intellectual disability
Sapir, T., Frotscher, M., Levy, T., Mandelkow, E., & Reiner, O. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr603 · Cited by 93
Making sense of the multiple MAP-2 transcripts and their role in the neuron
Shafit-Zagardo, B., & Kalcheva, N. (1998) · Molecular Neurobiology · doi:10.1007/bf02740642 · Cited by 89
Pro-aggregant Tau impairs mossy fiber plasticity due to structural changes and Ca++ dysregulation
Decker, J. M., Krüger, L., Sydow, A., Zhao, S., Frotscher, M., Mandelkow�, E., & Mandelkow, E. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0193-3 · Cited by 86
“However, in mature neurons Tau is largely restricted to axons, suggesting a presynaptic role [44,45].”
BackgroundFibronectin supports neurite outgrowth and axonal regeneration of adult brain neurons in vitro
Tonge, D. A., de Burgh, H. T., Docherty, R. J., Humphries, M. J., Craig, S. E., & Pizzey, J. A. (2012) · Brain Research · doi:10.1016/j.brainres.2012.03.024 · Cited by 78
Severt, W. L., Biber, T. U., Wu, X., Hecht, N. B., DeLorenzo, R. J., & Jakoi, E. R. (1999) · Journal of Cell Science · doi:10.1242/jcs.112.21.3691 · Cited by 78
Zhang, J., Dix, J., Langtimm, C. J., Trusk, T. C., Schroeder, B., Hoffmann, R. G., Strosberg, A. D., Winslow, J. W., & Sieber‐Blum, M. (1997) · Journal of Neurobiology · doi:10.1002/(sici)1097-4695(199703)32:3 · Cited by 33
Hole, K. L., & Williams, R. J. (2020) · Brain Plasticity · doi:10.3233/bpl-200098 · Cited by 81
“Hyperphosphorylation of tau promotes its mislocalization to the somatodendritic region [86] (Fig.”
BackgroundKaufmann, W. E. (2000) · Cerebral Cortex · doi:10.1093/cercor/10.10.992 · Cited by 75
Hall, G. F., Yao, J., & Lee, G. S. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4733 · Cited by 76
Cyclooxygenase-2 expression during rat neocortical development and in Rett syndrome
Kaufmann, W. E., Worley, P. F., Taylor, C. V., Bremer, M. E., & Isakson, P. C. (1997) · Brain and Development · doi:10.1016/s0387-7604(96)00047-2 · Cited by 73
Melková, K., Zapletal, V., Narasimhan, S., Jansen, S., Hritz, J., Škrabana, R., Zweckstetter, M., Jensen, M. R., Blackledge, M. J., & Žídek, L. (2019) · Biomolecules · doi:10.3390/biom9030105 · Cited by 78
“Transfection experiments suggested that the presence of long PD prevents MAP2a/b from entering the axons [6].”
BackgroundSayas, C. L., Tortosa, E., Bollati, F. A., Ramírez‐Ríos, S., Arnal, I., & Ávila, J. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13091 · Cited by 74
Estellés, A., Yokoyama, M., Nothias, F., Vincent, J., Glowinski, J., Vernier, P., & Chneiweiss, H. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.25.14800 · Cited by 70
Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons
Weissmann, C., Reyher, H.-J., Gauthier‐Kemper, A., Steinhoff, H., Junge, W., & Brandt, R. (2009) · Traffic · doi:10.1111/j.1600-0854.2009.00977.x · Cited by 71
Artificial confocal microscopy for deep label-free imaging
Chen, X., Kandel, M. E., He, S., Hu, C., Lee, Y. J., Sullivan, K. M., Tracy, G., Chung, H. J., Kong, H. J., Anastasio, M. A., et al. (2023) · Nature Photonics · doi:10.1038/s41566-022-01140-6 · Cited by 67
“We used two common stains to tag the Tau and MAP2 proteins 44 (see Methods) the ratios of which are a popular model for differentiating the long axon from smaller dendrites.”
MethodThe value of serum tau protein for the diagnosis of intracranial injury in minor head trauma
Kavalcı, C., Pekdemir, M., Durukan, P., İlhan, N., Yildiz, M., Serhatlıoğlu, S., & Seçkin, D. (2007) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2006.10.008 · Cited by 67
Application of novel vectors for GFP-tagging of proteins to study microtubule-associated proteins
Ludin, B., Doll, T., Meili, R., Kaech, S., & Matus, A. I. (1996) · Gene · doi:10.1016/0378-1119(95)00899-3 · Cited by 67
Lee, S., Kim, W., Li, Z., & Hall, G. F. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/172837 · Cited by 67
“This is consistent with reports that active targeting of tau to the axon occurs mainly at the mRNA rather than the protein level [60, 61] and with reports that tau may be slightly overexpressed in non-AD human tauopathies [62].”
ResultBiology of the Postsynaptic Glycine Receptor
Vannier, C., & Triller, A. (1997) · International review of cytology · doi:10.1016/s0074-7696(08)61611-3 · Cited by 60
Behind the curtain of tauopathy: a show of multiple players orchestrating tau toxicity
Huang, Y., Wu, Z., & Zhou, B. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2042-8 · Cited by 58
“Under normal physiological conditions, tau proteins are retained in the axon mainly due to the high affinity for axonal MT and low affinity for dendritic MT [86].”
Kong, J., Tung, V. W.-Y., Aghajanian, J. G., & Xu, Z. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.140.5.1167 · Cited by 57
“, 1997), and allow neurons to compartmentally regulate the distribution of a variety of cellular components, including cytoskeletal components (Kanai and Hirokawa, 1995; Kosik and Finch, 1987), ion channels, and receptors (Crino and Eberwine, 1996; Johnston et al.”
Kunimoto, M. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.131.6.1821 · Cited by 53
“So far, several possible mechanisms for the selective localization of tau in the axon and MAP2 in the dendrites have been suggested; first is the locally differing microtubule-binding affinities of the two proteins (Kanai and Hirokawa, 1995), second is the decreased transit of MAP2 in the axons (Kanai and Hirokawa, 19…”
Regulatory mechanisms for the axonal localization of tau protein in neurons
Iwata, M., Watanabe, S., Yamane, A., Miyasaka, T., & Misonou, H. (2019) · Molecular Biology of the Cell · doi:10.1091/mbc.e19-03-0183 · Cited by 51
“This was very surprising from its diffusive nature (Figure 6) and literature reporting the importance of MTBD in the axonal localization and transport of tau (Kanai and Hirokawa, 1995; Utton et al., 2005; Falzone et al., 2009; Weissmann et al., 2009; Li et al., 2011; Scholz and Mandelkow, 2014).”
BackgroundTerabayashi, T., Itoh, T. J., Yamaguchi, H., Yoshimura, Y., Funato, Y., Ohno, S., & Miki, H. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3986-07.2007 · Cited by 52
Insights into secretory and endocytic membrane traffic using green fluorescent protein chimeras
Lippincott‐Schwartz, J., & Smith, C. L. (1997) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(97)80082-7 · Cited by 52
Boda, B., Mas, C., Giudicelli, C., Népote, V., Guimiot, F., Levacher, B., Zvara, Á., Sántha, M., Gall, I. L., & Simonneau, M. (2004) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201217 · Cited by 50
Helbok, R., Schiefecker, A. J., Delazer, M., Beer, R., Bodner, T., Pfausler, B., Benke, T., Lackner, P., Fischer, M., Sohm, F., et al. (2014) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2013-307326 · Cited by 52
Takahashi, M., Tomizawa, K., & Ishiguro, K. (2000) · Brain Research · doi:10.1016/s0006-8993(99)02424-5 · Cited by 48
The tau proteins in neuronal growth and development
Brandt, R. (1996) · Frontiers in bioscience · doi:10.2741/a120 · Cited by 47
“Axonal localization of tau may also be caused by locally regulated microtubule binding (67, 68).”
BackgroundNormal dendritic arborization in spinal motoneurons requires neurofilament subunit L
Zhang, Z., Casey, D. M., Julien, J., & Xu, Z. (2002) · The Journal of Comparative Neurology · doi:10.1002/cne.10306 · Cited by 45
“…and Johnston, 1997; Markram et al., 1997), and allow neurons to compartmentally regulate the distribution of a variety of cellular components, including cytoskeleton (Kosik and Finch, 1987; Kanai and Hirokawa, 1995), ion channels, and receptors (Crino and Eberwine, 1996; Johnston et al., 1996).”
BackgroundDephosphorylation of tau during transient forebrain ischemia in the rat
Shackelford, D. A., & Yeh, R. Y. (1998) · Molecular and Chemical Neuropathology · doi:10.1007/bf02815073 · Cited by 40
“Dephosphorylatio n/phosphorylatio n of z is proposed to regulate its binding to microtubules and its preferential localization in axons (Lindwall and Cole, 1984; Drechsel et al., 1992; Biernat et al., 1993; Drewes et al., 1995; Kanai and Hirokawa, 1995 ).”
BackgroundTruncated tau deregulates synaptic markers in rat model for human tauopathy
Jadhav, S., Katina, S., Kováč, A., Kazmerova, Z., Novák, M., & Žilka, N. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00024 · Cited by 40
“This difference may be attributed to the regional binding affinity of tau and the preference to axonal tubulin binding activity in neurons (Kanai and Hirokawa, 1995).”
BackgroundSahara, N., Murayama, M., Higuchi, M., Suhara, T., & Takashima, A. (2014) · Frontiers in Neurology · doi:10.3389/fneur.2014.00026 · Cited by 37
Dendritic/Post-synaptic Tau and Early Pathology of Alzheimer’s Disease
Yin, X., Zhao, C., Qiu, Y., Zhou, Z., Bao, J., & Qian, W. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.671779 · Cited by 41
Transgenic Expression of Embryonic MAP2 in Adult Mouse Brain: Implications for Neuronal Polarization
Marsden, K. M., Doll, T., Ferralli, J., Botteri, F. M., & Matus, A. I. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-10-03265.1996 · Cited by 35
Defective axonal transport in motor neuron disease
El‐Kadi, A. M., Soura, V., & Hafezparast, M. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21188 · Cited by 34
“This is achieved partially by selective transport and stabilization of tau (an MAP) in axons and MAP2 in dendrites (Okabe and Hirokawa, 1989; Kanai and Hirokawa, 1995; Hirokawa et al., 1996).”
BackgroundBalaji, V., Kaniyappan, S., Mandelkow�, E., Wang, Y., & Mandelkow, E.-M. (2018) · Autophagy · doi:10.1080/15548627.2018.1509607 · Cited by 33
“On the protein level, mechanisms suggested for the axonal localization of MAPT included: (1) differential turnover of MAPT in axons and in somatodendritic compartments; (2) tighter binding of MAPT to microtubules in axons than in dendrites [14,15]; (3) preferential axonal transport of MAPT soon after its synthesis in…”
BackgroundMethodSerum Biomarkers of Neurologic Injury in Cardiac Operations
Seco, M., Edelman, J. J., Wilson, M. K., Bannon, P. G., & Vallely, M. P. (2012) · The Annals of Thoracic Surgery · doi:10.1016/j.athoracsur.2012.04.142 · Cited by 32
Schwab, Y., Mouton, J., Chasserot‐Golaz, S., Marty, I., Maulet, Y., & Jover, E. (2001) · Molecular Brain Research · doi:10.1016/s0169-328x(01)00244-3 · Cited by 32
Potentiation of Tau Aggregation by cdk5 and GSK3β
Lee, S., Hall, G. F., & Shea, T. B. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-102016 · Cited by 30
MAP2d promotes bundling and stabilization of both microtubules and microfilaments
Ferhat, L., Represa, A., Bernard, A., Ben-Ari, Y., & Khrestchatisky, M. (1996) · Journal of Cell Science · doi:10.1242/jcs.109.5.1095 · Cited by 30
Mechanisms of Axonal Sorting of Tau and Influence of the Axon Initial Segment on Tau Cell Polarity
Zempel, H., & Mandelkow�, E. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-32-9358-8_6 · Cited by 30
Teravskis, P. J., Ashe, K. H., & Liao, D. (2020) · The Neuroscientist · doi:10.1177/1073858420916696 · Cited by 31
“Expressing exogenous tau cDNA lacking native introns and untranslated regions (UTR) late in neuronal development leads to homogeneous distribution throughout cultured neurons (Hoover and others 2010; Kanai and Hirokawa 1995).”
BackgroundXie, C., Miyasaka, T., Yoshimura, S., Hatsuta, H., Yoshina, S., Kage-Nakadai, E., Mitani, S., Murayama, S., & Ihara, Y. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089796 · Cited by 28
“Microtubule-associated protein 2 (MAP2) and Tau differ notably in their subcellular localization within neurons: whereas Tau is distributed abundantly in the axonal compartment, MAP2 is found exclusively in the somatodendritic compartment [9,10].”
BackgroundMolecular diversity of neocortical GABAergic interneurones
Blatow, M., Caputi, A., & Monyer, H. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.078584 · Cited by 28
“In addition to detecting whether a protein is expressed in GABAergic interneurones or not, the availability of antibodies also permits localization studies with respect to defined cellular compartments (Kanai & Hirokawa, 1995; Waldvogel et al. 1999).”
BackgroundCellular Biology of Tau Diversity and Pathogenic Conformers
Kang, S., Eskandari‐Sedighi, G., Hromádková, L., Safar, J., & Westaway, D. A. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.590199 · Cited by 29
“Unlike MAP2 which is another major species of MAPs found in the neuronal bodies and dendrites, tau is abundant in the axon (35) (Figure 1B).”
BackgroundTau differentially regulates the transport of early endosomes and lysosomes
Balabanian, L., Lessard, D. V., Swaminathan, K., Yaninska, P., Sébastien, M., Wang, S., Stevens, P. W., Wiseman, P. W., Berger, C. L., & Hendricks, A. G. (2022) · Molecular Biology of the Cell · doi:10.1091/mbc.e22-01-0018 · Cited by 26
“Axonal microtubule bundles are heavily decorated with tau, yet robust intracellular transport in axons supports neuronal signaling and homeostasis (Kosik and Finch, 1987; Kanai and Hirokawa, 1995).”
Tau isoforms which contain the domain encoded by exon 6 and their role in neurite elongation
Luo, M., Leski, M. L., & Andreadis, A. (2004) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20029 · Cited by 27
“A tau proline-rich domain directly downstream of exon 6 is a substrate for kinases and indispensable for MT binding [Kanai and Hirokawa, 1995; Mandelkow et al., 1995; Goode et al., 1997].”
BackgroundEnhanced Tau Protein Translation by Hyper-Excitation
Kobayashi, S., Tanaka, T., Soeda, Y., & Takashima, A. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00322 · Cited by 22
KIF5C, a novel neuronal kinesin enriched in motor neurons
Kanai, Y. (2000) · Neuroscience Research · doi:10.1016/s0168-0102(00)81149-9 · Cited by 26
“We constructed deleted fragments of the clones by the conventional 3Ј deletion method using E xonuclease III /mung bean nuclease (TaKaRa, Tokyo, Japan) to read the entire sequence (Kanai et al., 1992; Kanai and Hirokawa , 1995).”
MethodSelf-citationYi, Y., Chang, Y., Li, S., Zhu, J., Wu, Y., Jiang, X., Li, L., Liu, R., Ma, R., & Li, G. (2023) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2023.110685 · Cited by 24
“As the affinity of tau to axonal microtubules is higher than that of postsynaptic structures including dendrites or soma in neurons, tau is predominantly localized to axons(3, 4).”
BackgroundThe specific targeting of guidance receptors within neurons: Who directs the directors?
Allen, J., & Chilton, J. K. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2008.12.013 · Cited by 24
Localization of calcitonin gene-related peptide mRNA in developing olfactory axons
Denis‐Donini, S., Branduardi, P., Campiglio, S., & Carnevali, C. (1998) · Cell and Tissue Research · doi:10.1007/s004410051158 · Cited by 23
“…is active transport along the cytoskeletal components (Singer 1992) and the integrity of microtubules has been shown to be necessary to maintain mRNA localization in different types of neurons (Litman et al. 1994; Bassel et al. 1994; Kanai and Hirokawa 1995; Olink-Coux and Hollenbeck 1996).”
BackgroundWozniak, M., & Limbird, L. E. (1998) · Brain Research · doi:10.1016/s0006-8993(97)01216-x · Cited by 21
Fujiwara, H., Watanabe, S., Iwata, M., Ueda, S., Nobuhara, M., Wada-Kakuda, S., Misonou, H., & Miyasaka, T. (2019) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2019.10.191 · Cited by 16
Miller, N. M., Shriver, L. P., Bodiga, V. L., Ray, A., Basu, S., Ahuja, R., Jana, A., Pahan, K., & Dittel, B. N. (2013) · ASN NEURO · doi:10.1042/an20120087 · Cited by 19
“To investigate this question, we stained neurons that had been exposed to lytic granules with anti-β3-tubulin (green) to stain microtubules in both axons and dendrites in combination with anti-MAP2 (blue) to mark dendrites and anti-ankyrin G (red) to mark axons (Figure 8) (Boiko et al., 2007; Kaech and Banker, 2006; K…”
BackgroundMethodQuantitative Analysis of MAP-Mediated Regulation of Microtubule Dynamic Instability In Vitro
Kiris, E., Ventimiglia, D., & Feinstein, S. C. (2010) · Methods in cell biology · doi:10.1016/s0091-679x(10)95024-3 · Cited by 19
Kristensson, K. (1996) · Brain Research Bulletin · doi:10.1016/s0361-9230(96)00255-9 · Cited by 19
MAP2 phosphorylation: mechanisms, functional consequences, and emerging insights
Lyu, J., DeMarco, A. G., Sweet, R. A., & Grubisha, M. J. (2025) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2025.1610371 · Cited by 20
“Furthermore, it prevents the entry of MAP2A and MAP2B into axons, thereby directing their localization to dendrites (Kanai and Hirokawa, 1995).”
Sayas, C. L., & Ávila, J. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-132315 · Cited by 15
Modeling tauopathy: a range of complementary approaches
Hall, G. F., & Yao, J. (2004) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.10.002 · Cited by 14
“Finally, primary neuron culture is an additional approach that can be taken to ensure that a fully differentiated neuronal phenotype is present, which can be a critical factor in studies of normal functions of tau, such as the developmental sorting of tau and other MAPs between axons and dendrites [28,29,119].”
BackgroundMicrotubule Organization and Microtubule-Associated Proteins (MAPs)
Tortosa, E., Kapitein, L. C., & Hoogenraad, C. C. (2016) · Springer eBooks · doi:10.1007/978-4-431-56050-0_3 · Cited by 13
“…due to a combination of several mechanisms, including dendrite-specific localization of MAP2 mRNA, suppression of MAP2 sorting into axons, and differential protein stability and turnover of MAP2 dendrites (Garner et al. 1988; Hirokawa et al. 1996; Kanai and Hirokawa 1995; Okabe and Hirokawa 1989).”
Metadata
- Authors
- Kanai, Y., & Hirokawa, N.
- Affiliations
- The University of Tokyo (JP)
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1995-02
- Volume
- 14
- Issue
- 2
- Pages
- 421-432
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2039754449
- Cited by
- 144
- References
- 70
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 7 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 7 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 7 · 2014: 6 · 2013: 4 · 2012: 6
- FWCI
- 5.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- tau protein, MAP2, MAP2c, axonal transport, microtubule binding, projection domain, tau phosphorylation, neuronal cytoskeleton, chimeric mutants
- MeSH terms
- Amino Acid Sequence, Animals, Axons, Cells, Cultured, Dendrites, Embryo, Mammalian, Fluorescent Antibody Technique, Microtubule-Associated Proteins, Microtubules, Molecular Sequence Data, Neurons, Protein Binding, Sheep, Spinal Cord, Transfection, Proto-Oncogene Proteins c-myc, tau Proteins, Sequence Homology, Amino Acid, In Situ Hybridization, Mice
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 ›
Are you an author, or do you see a problem with this page? Request a review
