Microtubule-associated proteins (MAPs) of the MAP2/Tau family include the vertebrate proteins MAP2, MAP4, and Tau and homologs in other animals. All three vertebrate members of the family have alternative splice forms; all isoforms share a conserved carboxy-terminal domain containing microtubule-binding repeats, and an amino-terminal projection domain of varying size. MAP2 and Tau are found in neurons, whereas MAP4 is present in many other tissues but is generally absent from neurons. Members of the family are best known for their microtubule-stabilizing activity and for proposed roles regulating microtubule networks in the axons and dendrites of neurons. Contrary to this simple, traditional view, accumulating evidence suggests a much broader range of functions, such as binding to filamentous (F) actin, recruitment of signaling proteins, and regulation of microtubule-mediated transport. Tau is also implicated in Alzheimer's disease and other dementias. The ability of MAP2 to interact with both microtubules and F-actin might be critical for neuromorphogenic processes, such as neurite initiation, during which networks of microtubules and F-actin are reorganized in a coordinated manner. Various upstream kinases and interacting proteins have been identified that regulate the microtubule-stabilizing activity of MAP2/Tau family proteins.
Gene organization and evolutionary history
Several types of microtubule-associated protein (MAP) have evolved in eukaryotes, including microtubule motors, microtubule plus-end-binding proteins, centrosome-associated proteins, enzymatically active MAPs, and structural MAPs. We focus here on the MAP2/Tau family of structural MAPs, which along with the MAP1A/1B family form one of the 'classical', well-characterized families of MAPs. In mammals, the family consists of the neuronal proteins MAP2 and Tau and the non-neuronal protein MAP4 (Table 1).
Table 1. Properties of human MAP2/Tau family genes
It has been proposed that the Escherichia coli protein ZipA, which interacts with the bacterial tubulin homolog FtsZ , might be an ancient prototype of MAP2/Tau family members . ZipA contains a region with limited homology to MAP2/Tau proteins, but this region is neither sufficient nor necessary for FtsZ binding . A single, unambiguous functional ortholog of MAP2/Tau proteins is found in Caenorhabditis elegans (alternative splice forms PTL-1A and PTL-1B [4,5]) and in Drosophila melanogaster (CG31O57 ; see Figure 1). Both contain microtubule-binding domains related to those in mammalian MAP2/Tau proteins. In contrast, the genome of the frog Xenopus laevis has an ortholog of each member of the family. At least three distinct MAP2/Tau related genes have been identified in the Tetraodon (pufferfish) genome: CAF98218 and CAGO9246 appear similar to MAP2, whereas CAGO3O2O appears similar to Tau . Additional MAP2/Tau-related genes appear to be present in Tetraodon, but the limited sequence information and lack of mapping data make it difficult to evaluate their significance. No homologs have been found in eukaryotes outside animals. Mammalian MAP2/Tau genes span multiple exons, which are spliced to produce several alternative isoforms [8,9] (Table 1 and see below).
Figure 1. Phylogenetic analysis of MAP2/Tau family proteins. Homologous protein sequences of the microtubule-binding repeats of MAP2 (using splice forms (with three microtubule-binding repeats), Tau (four-repeat isoforms), MAP4 (five-repeat isoforms) and the invertebrate MAPs CG31057 and PTL-1A (five-repeat isoforms) were analyzed using the program Phylip 76; gaps were ignored. The available Tetraodon sequences are incomplete and were therefore not included in the analysis.
Characteristic structural features
All MAP2/Tau family proteins have microtubule-binding repeats near the carboxyl terminus , each containing a conserved KXGS motif that can be phosphorylated (Figure 2) [11,12]. In addition, each family member contains an amino-terminal projection domain of varying size. In MAP2 and Tau, this domain has a net negative charge and exerts a long-range repulsive force as shown by atomic force microscopy . Each protein has several isoforms, with variation in the length of the projection domain and the number of microtubule-binding repeats [8,9]. The main forms of MAP2 are MAP2C, which is relatively short, and MAP2a and MAP2b, which have longer projection domains.
Figure 2. The domain organization of MAP2/Tau family proteins. Selected isoforms of the human members of the family are shown, as well as the nematode homolog PTL-1. All family members have alternative splice forms with varying numbers of carboxy-terminal microtubule-binding repeats and amino-terminal projection domains of varying lengths. PKA (RII) indicates a domain interacting with the RII subunit of protein kinase A. Repeats that are not present in all major isoforms are shown lighter.
MAP2/Tau family members are natively unfolded molecules and, like other proteins in this class, are thought to adopt specific conformations upon binding to their targets (microtubules, F-actin and potentially other molecules) . Most regions of MAP2/Tau proteins seem to be devoid of secondary structure. The only region of MAP2 that appears to form a secondary structure is an amino-terminal domain (residues 86-5103), which is found in all isoforms and interacts with the regulatory subunit of protein kinase A (PKA). Like the related domain in the A-kinase anchoring protein AKAP79/150, this region is predicted to form an amphipathic helix .
MAP2 also can interact directly with F-actin ; interestingly, the F-actin-binding site is located within the domain containing the microtubule-binding repeats. Although the MAP2 repeat region is highly similar to that of Tau, neither wild-type Tau nor MAP2 chimeras containing the Tau microtubule-binding repeats can bind to F-actin directly. However, F-actin binding is conferred on Tau if its microtubule-binding domain is exchanged for the corresponding region of MAP2 .
Localization and function
Developmental and regional expression
Mammalian MAP2 is expressed mainly in neurons, but MAP2 immunoreactivity is also detected in some non-neuronal cells such as oligodendrocytes. Its expression is very weak in neuronal precursors and then becomes strong about 1 day after expression of neuron-specific tubulin isoform βIII . MAP2c is the juvenile isoform and is downregulated after the early stages of neuronal development , whereas MAP2b is expressed both during development and adulthood. MAP2a becomes expressed when MAP2c levels are falling and is not detected uniformly in all mature neurons . In the brain, smaller splice forms of Tau (of 50-565 kDa) are differentially expressed during early development. Specifically, Tau isoforms with three microtubule-binding repeats are predominantly expressed during early development, whereas isoforms with four repeats are expressed during adulthood [20,21]. High-molecular-weight variants of Tau (110-5120 kDa) are expressed in peripheral neurons and also at a much lower level in the brain . MAP4 is expressed in various organs, including brain, adrenal gland, lung and liver , but it is not ubiquitously expressed: in the brain, for example, MAP4 is expressed only in non-neuronal cells and is absent from neurons .
Shortly after axonogenesis in developing cortical and hippocampal neuronal cultures, Tau gradually segregates into axons, while MAP2 segregates into the nascent dendrites (at this stage dendrite precursors are called 'minor neurites') . It is believed that a combination of protein stability , differential protein sorting , and dendrite-specific transport of MAP2 mRNA  are responsible for this spatial segregation of the two MAPs. Thus, in mature neurons Tau is present mainly in axons whereas MAP2 is restricted to cell bodies and dendrites (Figure 3).
Figure 3. A neuron from a culture of rat brain hippocampus, showing the distinct subdomains of MAP2 and Tau enrichment in mature neurons. MAP2 is found specifically in dendrites (arrow), whereas Tau is mainly axonal (arrowhead). Note the fine meshwork of axons from neighboring cells outside the field of view that make numerous synaptic connections among the neurons in the culture.
Functions of MAP2 and Tau in neurons
MAP2/Tau family proteins were originally discovered for and characterized by their ability to bind and stabilize microtubules. Ultrastructural analyses revealed the presence of these MAPs along the sides of microtubules [29-31]. MAP2 and Tau also increase microtubule rigidity  and induce microtubule bundles in heterologous cell systems [33-35]. Microtubule bundle formation induced by MAP2 was suggested to be an indirect effect of its stabilization of microtubules within the confinement of cell borders , but more recent results suggest that MAP2-induced bundles can form even within the interior of the cell , indicating the existence of crosslinks. Evidence for direct crosslinking of microtubules by MAP2/Tau family proteins is lacking, leaving open the possibility that additional proteins are necessary.
As described above, MAP2 can bind both microtubules and F-actin, and both activities have been mapped to its microtubule-binding-repeat domain. It is not yet known whether a single molecule can crosslink an actin filament to a microtubule. MAP2 can bundle actin filaments in vitro . MAP2c by itself can induce neurites in Neuro-2a neuroblastoma cells; its microtubule-stabilizing activity is necessary for this effect but is not sufficient, and F-actin dynamics also need to be altered . MAP2's ability to interact with F-actin appears to be key to this specific biological function. Unlike MAP2C, neither Tau nor chimeric MAP2C containing the Tau microtubule-binding domain can trigger neurite initiation, an observation that correlates with their lack of F-actin binding in vitro . This suggests that MAP2c's ability to interact with both microtubules and F-actin is essential for its neurite-initiation activity.
Knockout experiments in mice suggest that neither MAP2 nor Tau is essential by itself, but each single knockout leads to detectable morphological phenotypes. Tau expression was undetectable after targeted deletion of the first Tau exon, which includes the protein start codon . Homozygous animals showed no major defects in brain morphology, but the microtubule density in small-caliber axons was reduced. Similarly, MAP2 expression was undetectable after deletion of one exon encoding a portion of the MAP2 microtubule-binding domain . Again, homozygous animals showed no major defects in brain morphology, but microtubule density in dendrites was reduced. In addition, dendrite length in cultured neurons was reduced, suggesting a role for MAP2 in supporting dendrite elongation.
The phenotypes of single knockouts suggest specific but nonessential roles for Tau and MAP2 in the morphogenesis of the nervous system. However, these proteins probably have multiple roles in other pathways and can be compensated for by other proteins with redundant functions. Interestingly, the structurally unrelated microtubule-associated protein MAP1B appears to have some redundant roles with both Tau [41,42] and MAP2 . Simultaneous inhibition of either MAP1B and Tau or MAP1B and MAP2 resulted in more severe phenotypes than those seen in single knockouts. Taken together, these experiments suggest a role for Tau, MAP2 and MAP1B in both neuronal migration and outgrowth of neurites. Redundancy among MAP2, Tau and MAP4 has not been adequately tested in mammalian systems. It is also possible that other classes of MAP such as stable tubule only protein (STOP), adenomatous polyposis coli (APC), doublecortin, or spectraplakins might provide additional redundancy with MAP functions.
MAP2/Tau family proteins have been shown to interact with numerous proteins; Table 2 provides an overview of identified interaction partners and briefly describes the proposed function of each interaction. Binding of MAP2 to the RII regulatory subunit of PKA is one of the best-characterized examples of a classical MAP functioning as an adaptor protein. The interaction site was mapped to the amino terminus of MAP2 and is present in all common MAP2 splice forms in mammals  but absent in Tau. Knockout mice show that MAP2 is essential for linking PKA to microtubules in various brain regions . Interestingly, the absence of MAP2 affects the phosphorylation of cAMP-responsive element binding protein (CREB), suggesting a role for the MAP2-PKA interaction in CREB-mediated signal transduction . Deletion of the PKA-binding site in MAP2c reduces its ability to induce neurites in neuroblastoma cells .
Table 2. Selected interaction partners of MAP2/Tau family proteins
Tau has been studied extensively for its involvement in neurofibrillary tangle formation in Alzheimer's Disease and in frontotemporal dementias associated with chromosome 17 (FTDP-17); see several excellent discussions of Tau pathology [45-48].
Functions of MAP4 and non-neuronal functions of MAP2 and Tau
The widely expressed non-neuronal member of the MAP2/Tau family, MAP4, shares many features with other members of the family, including the presence of microtubule-binding repeats  and microtubule-stabilizing activity . MAP4 has been proposed to play a role in regulating mitotic microtubule dynamics during metaphase . However, using function-blocking antibodies that interfere with the MAP4-microtubule interaction, a more recent study  failed to detect an obvious phenotype in mitosis or during interphase, suggesting that MAP4 might be a component of a functionally redundant system. Muscle-specific MAP4 isoforms have been shown to be required for myogenesis , but the exact role of MAP4 is not known in this process.
Although MAP2 is primarily neuronal, some isoforms are also present in certain astrocytes , oligodendrocytes , as well as in the testis . The testicular isoform of MAP2 contains a functional nuclear localization sequence  and is enriched in nuclei of germ cells. Like MAP2, the primarily neuronal Tau is also expressed in oligodendrocytes . Interestingly, alternative splicing of MAP2  and Tau  is similar during the maturation of oligodendrocytes and neurons. In oligodendrocytes, Tau and its regulation by the Fyn tyrosine kinase are proposed to be involved in process outgrowth .
Mechanism and regulation
Microtubules exhibit dynamic instability, an intrinsic behavior characterized by alternating phases of growth, shortening, and pausing. The switch from growth to shortening and the switch from shortening to growth are called catastrophes and rescues, respectively. MAP2/Tau proteins bind along the length of microtubules and stabilize microtubules by altering this dynamic behavior [31,60,61]. The small isoform MAP2c stabilizes microtubules primarily by reducing the frequency and duration of catastrophes . Under conditions where its concentration is non-saturating, MAP2 can also form clusters on microtubules, and microtubule catastrophes stop at such clusters . Interestingly, isoforms of Tau containing three or four microtubule-binding repeats have distinct effects on microtubule dynamics, with four-repeat isoforms protecting microtubules from depolymerization much more robustly than three-repeat isoforms . In cells, microtubules still exhibit dynamic behavior even when stabilizing MAPs are highly expressed , perhaps because their binding is regulated by phosphorylation and other factors.
A detailed cryo-electron microscopy (cryo-EM) analysis has suggested a possible mechanism by which MAP2/Tau might reduce catastrophes and thus stabilize microtubules. This study revealed that the microtubule-binding repeats interact in an elongated fashion on the outer microtubule lattice, spanning two tubulin dimers along a single protofilament rather than bridging adjacent protofilaments . Tau appeared to show a similar pattern. Several other experiments confirm that MAP2 binds to the outside of microtubules in vivo. First, the projection domain of MAP2 can regulate microtubule spacing . In addition, an EM study that compared wild-type to knockout animals suggested that electron-dense structures on the outer surface of microtubules contain MAP2 . Another cryo-EM analysis suggested that Tau binds to the inner surface of microtubules , but the role of this binding is not yet clear. Tau might be able to bind to multiple sites, both inside and outside the microtubule lattice. This idea is consistent with the observation that Tau has different kinetic properties when bound to pre-polymerized microtubules than when co-polymerized with microtubules .
MAP2/Tau family proteins can inhibit kinesin- and dynein-dependent transport along microtubules [67-71]. Observations in vitro suggest that this inhibition of microtubule motor activity occurs by direct competition of MAP2/Tau proteins with dynein and kinesin for microtubule binding and also suggest a major role for the projection domain of the MAP2/Tau proteins in this competition [69,71]. In cells, overexpression of Tau interferes with kinesin-based transport and alters the balance of plus-end- versus minus-end-directed transport [67,68]. In vivo, the MAP2 and Tau projection domains appear to be involved in regulating microtubule spacing . Such control over microtubule spacing might facilitate efficient organelle transport.
Binding of MAP2/Tau family proteins to microtubules can be regulated by phosphorylation of the KXGS motif within each microtubule-binding repeat. For both MAP2 and Tau, these motifs are phosphorylated by multiple protein kinases, including PKA  and the microtubule affinity regulating kinase (MARK) , and phosphorylation leads to decreased affinity for microtubules. Recent evidence also links the Jun kinase (Jnk) pathway to phosphorylation of MAP2 . Many other protein kinases can phosphorylate MAP2/Tau proteins in vitro, but for most the identity of the targeted residues in vivo and the functional consequences of phosphorylation remain to be determined. For example, in the olfactory bulb, a site in the amino-terminal domain of MAP2 is phosphorylated in vivo in a manner that is regulated by sensory-driven neural activity; the function of this phosphorylation is not yet known, however . The regulation of MAPs, including the MAP2/Tau family, has been summarized in a comprehensive review .
Since their original identification over 20 years ago, classical structural MAPs of the MAP2/Tau family have been extensively characterized in vitro and in vivo. A major challenge for further illuminating their function is the vast number of interaction partners and protein kinases predicted and confirmed to phosphorylate MAP2/Tau proteins. Although some key pathways controlling their activity have been elucidated, a broader and more precise analysis of phosphorylation and other post-translational modifications is needed to fully understand MAP2/Tau protein function in signaling networks controlling the morphogenesis of neurons. Recent progress in understanding the molecular mechanisms underlying MAP-microtubule and MAP-actin interactions in vitro is promising, but biological functions remain elusive. Future studies will need to correlate the effects of MAP2/Tau proteins in vivo with molecular knowledge gained from in vitro analyses. The apparent functional redundancies and cross-talk with other MAPs and cytoskeletal regulators are challenges that will require creative experimental strategies if we are to elucidate the specific functions of MAP2/Tau family proteins in cytoskeletal organization and morphological change.
We thank Julia Braga for preparation of the neuronal cultures shown in Figure 3. This work was supported by grants from the National Institutes of Health.
Cell 1997, 88:175-185.
The interaction between the bacterial tubulin homolog FtsZ and an ancestral MAP, ZipA, is described.PubMed Abstract | Publisher Full Text
EMBO J 1999, 18:2372-2383.
The functional significance of the ancestral MAP ZipA in bacterial cell division is described and its relation to MAP2/Tau is proposed.PubMed Abstract | Publisher Full Text
J Bacteriol 2000, 182:5153-5166.
The FtsZ interaction domain on ZipA is mapped to its carboxyl terminus, a region unrelated to MAP2/Tau, suggesting that ZipA is not a functional homolog of MAP2/Tau proteins.PubMed Abstract | Publisher Full Text | PubMed Central Full Text
J Cell Sci 1996, 109:2661-2672.
Describes the cloning of a MAP2/Tau homolog from C. elegans, expression analyses, microtubule binding and stabilization experiments, and overexpression studies.PubMed Abstract | Publisher Full Text
Biochemistry 1996, 35:9415-9423.
The first characterization and cloning of the C. elegans MAP2/Tau homolog.PubMed Abstract | Publisher Full Text
Mech Dev 2001, 108:171-178.
Cloning, expression and subcellular localization studies of the fly MAP2/Tau homolog are described.PubMed Abstract | Publisher Full Text
Proc Natl Acad Sci USA 1995, 92:10894-10898.
The human MAP2 gene is sequenced and analyzed and additional splice forms are characterized.PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Mol Cell Biol 1989, 9:1389-1396.
The bovine Tau gene is sequenced and analyzed and additional splice forms are described.PubMed Abstract | PubMed Central Full Text
Science 1988, 242:936-939.
This paper defined the relationship between MAP2 and Tau and thereby defined the MAP2/Tau family by showing that the two proteins contain related microtubule-binding domains.PubMed Abstract
Mol Biol Cell 2000, 11:3573-3587.
The phosphorylation of MAP2c by PKA and its relevance for MAP2-microtubule and MAP2-F-actin interaction is reported.PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Drewes G, Trinczek B, Illenberger S, Biernat J, Schmitt-Ulms G, Meyer HE, Mandelkow EM, Mandelkow E: Microtubule-associated protein/microtubule affinity-regulating kinase (p110mark). A novel protein kinase that regulates tau-microtubule interactions and dynamic instability by phosphorylation at the Alzheimer-specific site serine 262.
J Biol Chem 1995, 270:7679-7688.
Purification of a novel kinase and characterization of its role in regulating the microtubule-Tau interaction.PubMed Abstract | Publisher Full Text
FEBS Lett 2001, 505:374-378.
The authors measured a repulsive, entropic force generated by arrays of bovine brain MAPs (of which 70% was made up of the MAP2a and MAP2b isoforms).PubMed Abstract | Publisher Full Text
Eur J Biochem 2002, 269:2-12.
A review of the basic biochemical characteristics of natively unfolded proteins, such as the MAP2/Tau proteins.PubMed Abstract | Publisher Full Text
Biochem Biophys Res Commun 2003, 301:136-142.
Characterization of the structural properties of the PKA-RII-binding domain of MAP2 using limited proteolysis, nuclear magnetic resonance spectroscopy and circular dichroism spectroscopy.PubMed Abstract | Publisher Full Text
Curr Biol 2004, 14:363-371.
This key paper demonstrates that binding of MAP2/Tau proteins to F-actin correlates with their ability to induce neurites. It is also the first paper to measure this binding quantitatively.PubMed Abstract | Publisher Full Text
J Neurosci 1994, 14:5399-5416.
The temporal sequence of expression of neuronal markers β-III-tubulin and MAP2 is analyzed with respect to the behavior of migrating neurons and dividing neuronal precursors in the developing brain.PubMed Abstract | Publisher Full Text
J Neurochem 1988, 50:609-615.
The cloning and characterization of the small MAP2 isoform MAP2c is reported.PubMed Abstract
J Neurochem 1996, 66:1273-1281.
The cloning and characterization of the alternatively spliced adult MAP2 isoform MAP2a is described.PubMed Abstract | Publisher Full Text
Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA: Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease.
Neuron 1989, 3:519-26.
Characterization using RNAse protection assays of developmentally regulated isoforms of Tau that differ in the number of microtubule-binding repeats.PubMed Abstract | Publisher Full Text
Neuron 1989, 2:1389-1397.
Identification of isoforms of Tau and their developmental expression, using northern blots.PubMed Abstract | Publisher Full Text
J Neurochem 1994, 63:2300-2306.
An analysis of the regional expression of specific high-molecular-weight Tau splice forms.PubMed Abstract | Publisher Full Text
Kotani S, Murofushi H, Maekawa S, Aizawa H, Sakai H: Isolation of rat liver microtubule-associated proteins. Evidence for a family of microtubule-associated proteins with molecular mass of around 200,000 which distribute widely among mammalian cells.
J Biol Chem 1988, 263:5385-5389.
Cloning of MAP4 and analysis of its tissue expression.PubMed Abstract | Publisher Full Text
Neuroscience 1985, 15:869-875.
The expression of MAP4 in the murine brain is analyzed.PubMed Abstract | Publisher Full Text
J Physiol (Paris) 1990, 84:134-137.
A review of the subcellular localization and expression patterns of MAP2/Tau family proteins.PubMed Abstract
Hirokawa N, Funakoshi T, Sato-Harada R, Kanai Y: Selective stabilization of tau in axons and microtubule-associated protein 2C in cell bodies and dendrites contributes to polarized localization of cytoskeletal proteins in mature neurons.
J Cell Biol 1996, 132:667-679.
The stability of Tau and MAP2c in axons and dendrites was measured by injection of biotinylated exogenous proteins.PubMed Abstract | Publisher Full Text
Neuron 1995, 14:421-432.
This study uses mutational analysis to examine the differential sorting of MAP2 and Tau into axons or dendrites.PubMed Abstract | Publisher Full Text
Nature 1988, 336:674-677.
The localization of MAP2 mRNA to dendrites is reported.PubMed Abstract | Publisher Full Text
J Cell Biol 1988, 107:1449-1459.
An ultrastructural analysis of Tau binding to microtubules is reported.PubMed Abstract | Publisher Full Text
Hirokawa N, Hisanaga S-I, Shiomura Y: MAP2 is a component of crossbridges between microtubules and neurofilaments in the neuronal cytoskeleton: quick-freeze, deep-etch immunoelectron microscopy and reconstitution studies.
J Neurosci 1988, 8:2769-2779.
The structure of MAP2 in microtubule arrays is characterized using electron microscopy.PubMed Abstract | Publisher Full Text
J Cell Biol 2002, 157:1187-1196.
This paper is the first direct visualization of the structure of MAP2 and Tau on microtubules at 20 Å resolution using cryo-electron microscopy.PubMed Abstract | Publisher Full Text
J Cell Biol 1997, 138:1067-1075.
An analysis of the molecular basis of MAP2/Tau-induced flexural rigidity of microtubules using optical tweezers.PubMed Abstract | Publisher Full Text
Development 1992, 116:1151-1161.
The organization of microtubules in non-neuronal cells exogenously expressing MAP2c.PubMed Abstract | Publisher Full Text
Nature 1989, 342:498-505.
This paper describes microtubule bundle formation in transfected cells induced by MAP2 and Tau, and a potential mechanism is proposed. See also .PubMed Abstract | Publisher Full Text
Nature 1990, 345:674.
A letter providing additional data leading to a reinterpretation of the proposal in .PubMed Abstract | Publisher Full Text
Mol Biol Cell 1994, 5:511-517.
Given the lack of a high-affinity dimerization site on MAP2c, this article proposes that microtubule stabilization by itself, through the physical restraint of the cell borders, is responsible for microtubule bundling.PubMed Abstract | PubMed Central Full Text
Mol Biol Cell 1995, 6:981-996.
MAP2c-induced microtubule bundle assembly is analyzed by live-cell microscopy and the polarity of the resulting bundles is determined by electron microscopy.PubMed Abstract | PubMed Central Full Text
J Neurosci 2003, 23:9479-9490.
Cytoskeletal rearrangements during spontaneous and MAP2c-induced neurite initiation are characterized using live-cell microscopy and MAP2 deletion analysis.PubMed Abstract | Publisher Full Text
Nature 1994, 369:488-491.
Generation and characterization of a Tau knockout mouse, which has defects in axon ultrastructure.PubMed Abstract | Publisher Full Text
J Cell Biol 2002, 158:541-549.
MAP2 knockout mice show defects in dendrite outgrowth and targeting of the RII subunit of PKA to dendrites.PubMed Abstract | Publisher Full Text
J Cell Sci 1996, 109:467-477.
The results of inhibition of MAP1B and Tau expression by antisense oligonucleotides suggests functional redundancy of the two proteins.PubMed Abstract | Publisher Full Text
J Cell Biol 2000, 150:989-1000.
This paper reports the crossing of MAP1B and Tau knockout animals; anatomical analysis shows defects in axon outgrowth and neuronal migration.PubMed Abstract | Publisher Full Text
J Cell Biol 2001, 155:65-76.
The first MAP2 knockout mouse is described. Crossing of MAP1B and MAP2 knockout animals leads to defects in dendrite outgrowth and neuronal migration.PubMed Abstract | Publisher Full Text
Neuron 1989, 3:639-645.
Mapping of the PKA-RII-binding domain on MAP2 is reported.PubMed Abstract | Publisher Full Text
Annu Rev Neurosci 2001, 24:1121-1159.
This review gives a general overview of tauopathies, diseases thought to be linked to alterations in Tau behavior.PubMed Abstract | Publisher Full Text
Biochemistry 2003, 42:15009-15017.
A review of biochemical analyses of Tau polymerization and its relevance for tauopathies.PubMed Abstract | Publisher Full Text
Neuron 2003, 40:457-460.
A review of the role of Tau phosphorylation in neurodegenerative diseases.PubMed Abstract | Publisher Full Text
Ann NY Acad Sci 2000, 920:74-83.
The role of Tau mutations in the specific tauopathy FTDP-17 is reviewed.PubMed Abstract | Publisher Full Text
J Cell Sci 1991, 98:27-36.
This paper reports the cloning of MAP4 and comparison of its sequence with MAP2 and Tau.PubMed Abstract
J Cell Sci 1997, 110:281-294.
Stabilization of cellular microtubules by MAP4 is reported.PubMed Abstract | Publisher Full Text
Ookata K, Hisanaga S, Bulinski JC, Murofushi H, Aizawa H, Itoh TJ, Hotani H, Okumura E, Tachibana K, Kishimoto T: Cyclin B interaction with microtubule-associated protein 4 (MAP4) targets p34cdc2 kinase to microtubules and is a potential regulator of M-phase microtubule dynamics.
J Cell Biol 1995, 128:849-862.
This study reports an interaction of MAP4 with cyclin B and discusses its potential functional relevance for regulation of microtubules during mitosis.PubMed Abstract | Publisher Full Text
J Cell Biol 1996, 132:345-357.
In cultured cells, MAP4 was blocked using a function-blocking antibody. No phenotype was detected, suggesting that MAP4 is a component of a functionally redundant system.PubMed Abstract | Publisher Full Text
Development 1996, 122:771-781.
Defects in myogenesis in a muscle cell line lacking the muscle-specific MAP4 isoform were found.PubMed Abstract | Publisher Full Text
J Neurosci 1986, 6:1748-1756.
A report of the expression of MAP2 in specific astrocytes.PubMed Abstract | Publisher Full Text
J Neurosci Res 1995, 42:803-817.
The expression of the early neuronal MAP2 isoform MAP2c is analyzed during oligodendrocyte differentiation.PubMed Abstract
Loveland KL, Herszfeld D, Chu B, Rames E, Christy E, Briggs LJ, Shakri R, de Kretser DM, Jans DA: Novel low molecular weight microtubule-associated protein-2 isoforms contain a functional nuclear localization sequence.
J Biol Chem 1999, 274:19261-19268.
The discovery of nuclear MAP2 isoforms containing an alternatively spliced nuclear localization sequence.PubMed Abstract | Publisher Full Text
Proc Natl Acad Sci USA 1995, 92:10369-10373.
Expression of Tau in oligodendrocytes.PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Cell Tissue Res 1997, 288:239-249.
Expression of both Tau and MAP2 was analyzed in oligodendrocytes and compared to neurons.PubMed Abstract | Publisher Full Text
J Neurosci 2002, 22:698-707.
The role of an interaction between Fyn and Tau is analyzed.PubMed Abstract | Publisher Full Text
Biochemistry 1996, 35:12576-12586.
A study of the effect of purified, recombinant MAP2c on microtubule dynamics in vitro.PubMed Abstract | Publisher Full Text
Proc Natl Acad Sci USA 2003, 100:9548-9553.
The effects of different Tau isoforms on microtubule dynamics are reported and the relevance for neurodegenerative diseases is discussed.PubMed Abstract | Publisher Full Text | PubMed Central Full Text
J Mol Biol 2001, 312:107-118.
An analysis of the clustering of MAP2 on microtubules and its relevance for microtubule dynamics.PubMed Abstract | Publisher Full Text
Neuron 1996, 17:1189-1199.
The short- and long-term dynamics of microtubules in the presence of MAP2 or Tau are characterized.PubMed Abstract | Publisher Full Text
Nature 1992, 360:674-677.
Characterization of the role of MAP2 and Tau projection domains in microtubule spacing in axons and dendrites.PubMed Abstract | Publisher Full Text
EMBO J 2003, 22:70-77.
A cryo-EM study that reports the binding of Tau to the inner surface of microtubules.PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Proc Natl Acad Sci USA 2004, 101:6746-6751.
Tau binding to preassembled microtubules is compared to Tau binding after co-assembly with microtubules. The results suggest that Tau can bind microtubules in two distinct ways.PubMed Abstract | Publisher Full Text | PubMed Central Full Text
J Cell Sci 1999, 112:2355-2367.
The effect of Tau on dynein- and kinesin-dependent cellular transport processes is reported.PubMed Abstract | Publisher Full Text
Ebneth A, Godemann R, Stamer K, Illenberger S, Trinczek B, Mandelkow E: Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer's disease.
J Cell Biol 1998, 143:777-794.
The effect of Tau overexpression on kinesin-dependent transport processes is reported.PubMed Abstract | Publisher Full Text
J Biol Chem 1994, 269:3581-3589.
A biochemical analysis of competition between MAPs and microtubule motors.PubMed Abstract | Publisher Full Text
EMBO J 2002, 21:4896-4905.
Single-molecule analysis of kinesin movements on microtubules and the influence of Tau on movement parameters are measured.PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Cell Motil Cytoskeleton 1993, 24:1-16.
The effect of MAP2 and Tau on dynein and kinesin activity is measured using microtubule sliding assays.PubMed Abstract
Dev Cell 2003, 4:521-533.
This report shows a reduced association of MAP2 with microtubules in Jnk1 knockout mice.PubMed Abstract | Publisher Full Text
J Neurosci 1997, 17:9596-9604.
A report of activity-dependent phosphorylation of a specific site on MAP2.PubMed Abstract | Publisher Full Text
Int Rev Cytol 2001, 210:163-226.
This substantial review summarizes the activity and regulation of animal cell MAPs, including Tau and MAP2.PubMed Abstract
J Cell Biol 1979, 80:266-276.
A highly enriched MAP2 fraction was prepared from calf neurotubules and a MAP2-microtubule interaction and microtubule stabilization were found.PubMed Abstract | Publisher Full Text
J Biol Chem 2000, 275:20578-20587.
A report of the interaction of MAP2 with Src and Grb2 and regulation of this interaction by Erk2.PubMed Abstract | Publisher Full Text
J Biol Chem 2001, 276:39950-39958.
A report of the interaction of Fyn with MAP2c and the regulation of this interaction by Erk2.PubMed Abstract | Publisher Full Text
J Cell Biol 1982, 95:982-986.
An interaction of MAP2 with neurofilaments is reported.PubMed Abstract | Publisher Full Text
J Biol Chem 1999, 274:30280-30287.
This paper describes a role for MAP2 as an AKAP (A-kinase anchoring protein) for class C L-type calcium channels.PubMed Abstract | Publisher Full Text
Brain Res Mol Brain Res 2000, 79:192-201.
Two proteins were cloned that interact specifically with MAP2 mRNA elements responsible for dendritic targeting.PubMed Abstract | Publisher Full Text
J Cell Biol 1991, 115:717-730.
Mapping of the microtubule binding site of Tau.PubMed Abstract | Publisher Full Text
J Cell Sci 1998, 111:3167-3177.
The interaction between Fyn and Tau is reported.PubMed Abstract | Publisher Full Text
Takashima A, Murayama M, Murayama O, Kohno T, Honda T, Yasutake K, Nihonmatsu N, Mercken M, Yamaguchi H, Sugihara S, Wolozin B: Presenilin 1 associates with glycogen synthase kinase-3beta and its substrate tau.
Proc Natl Acad Sci USA 1998, 95:9637-9641.
A report of the interaction of Presenilin 1 with GSK3-beta and Tau.PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Strittmatter WJ, Saunders AM, Goedert M, Weisgraber KH, Dong LM, Jakes R, Huang DY, Pericak-Vance M, Schmechel D, Roses AD: Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease.
Proc Natl Acad Sci USA 1994, 91:11183-11186.
A report of the interaction between ApoE and Tau.PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Baudier J, Mochly-Rosen D, Newton A, Lee SH, Koshland DE Jr, Cole RD: Comparison of S100b protein with calmodulin: interactions with melittin and microtubule-associated tau proteins and inhibition of phosphorylation of tau proteins by protein kinase C.
Biochemistry 1987, 26:2886-2893.
The interaction between S100b and Tau is reported.PubMed Abstract