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Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bovine microtubule protein preparations have been examined by proton nuclear magnetic resonance (1H NMR) spectroscopy at 270 MHz. Sharp resonances have been identified as deriving from microtubule-associated proteins. These resonances persist after self-assembly of microtubule protein. Brief tryptic treatment of assembled microtubules, specifically cleaving the microtubule-associated protein HMW2 (Mr = 270 000), releases the pendant portion of HMW2 (Mr = 240 000), three-quarters of which is in a flexible conformation. Isolated tau protein and HMW2 protein both show substantial flexibility; on recombination with tubulin dimer, tau shows considerable decrease in flexibility whereas HMW2 is unaffected. The observations may have important implications for the interactions between microtubules and other cytoskeletal structures.
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PMID:Molecular flexibility in microtubule proteins: proton nuclear magnetic resonance characterization. 686 Jun 59

The axonal microtubule-associated protein, tau, is thought to play an important role in axonal growth and in the establishment of neuronal polarity. In adult human brain there are six alternatively spliced tau isoforms, which have different microtubule binding affinities in vitro. The tubulin-tau interaction is further modified by phosphorylation of tau and, compared to adult brain tau, both foetal brain tau and paired helical filament (PHF) tau, characteristic of Alzheimer's disease, are hyperphosphorylated. In vivo both the expression of tau isoforms and their phosphorylation states are developmentally regulated. In order to establish the correlation between the expression of tau isoforms and their pattern of phosphorylation, we have characterised these two features in several in vitro models of neuronal differentiation, including the human neuroblastoma cell lines, SK-N-SH, SH-SY5Y and IMR32 cells, rat PC12 cells and primary rat cortical neurones. Sensitive RT-PCR analysis revealed a different complement of tau isoforms in the different cell lines and neuritogenesis was associated mainly with an increase in the overall tau protein level with no apparent phosphorylation changes. A switch in tau isoform expression occurred only at the terminal stages of neuronal development, when it may be important in reinforcing the previously established axonal cytoarchitecture.
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PMID:Tau isoform expression and phosphorylation state during differentiation of cultured neuronal cells. 749 9

Adult human nerve cells contain tau protein, a phosphorylated microtubule-associated protein, that is hyperphosphorylated in the fetus and in patients with Alzheimer's disease. Hyperphosphorylation, which diminishes the microtubule-binding capacity of tau, destabilizes microtubules and may enhance the formation of paired helical filaments that constitute neurofibrillary tangles in Alzheimer's disease. Here, we use phosphorylation-dependent anti-tau antibodies to detect specific epitopes that characterize hyperphosphorylated tau. Our demonstration of intracellular tangles containing full-length tau that are not immunolabeled by these antibodies suggests that hyperphosphorylation of tau is not obligatory in the formation of neurofibrillary tangles in Alzheimer's disease.
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PMID:Absence of abnormal hyperphosphorylation of tau in intracellular tangles in Alzheimer's disease. 766 54

Cyclin dependent kinase 5 (Cdk5) phosphorylates tau protein, a microtubule-associated protein, at pathological sites in vitro as well as in Alzheimer's disease brain. The enzyme is therefore regarded as an important candidate responsible for the progression of Alzheimer's disease. We and others have suggested that the enzyme has physiological roles in brain development and maturation. In this study, we investigated the exact distribution and developmental changes of the enzyme in cerebellum by immunohistochemistry and non-radioactive in situ hybridization. Immunohistochemistry demonstrated that Cdk5 was consistently expressed in the cerebellum at all developing stages. However, the subcellular localization of Cdk5 dramatically changed during maturation of the cerebellum. In the early neonatal stage, Cdk5 was strongly expressed in the cell bodies of neurones. With neuronal maturation Cdk5 immunoreactivity changed its subcellular localization from the cell body to axon. In terminally differentiated neurons, the immunoreactivity was only detected in the axon. These results suggest that subcellular localization of Cdk5 is strictly regulated and may play an important role in neuronal maturation.
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PMID:Developmental changes of cyclin dependent kinase 5 subcellular localization in the rat cerebellum. 766 83

Neuronal hybrid ND 7/23 cells, which display sensorylike properties, develop neurites when cultured in the presence of either dibutyryl cyclic AMP plus nerve growth factor (DBcAMP + NGF) or retinoic acid or a phorbol ester derivative, although they express only trace amounts of the microtubule-associated tau proteins and low levels of microtubule-associated protein 2c (MAP2c). Nondifferentiated ND cells transfected with tau cDNAs did not develop neurites, whereas very short cell processes were formed in MAP2c-transfected cells. tau and MAP2 antibodies labeled microtubule bundles displayed in a ring array underneath the surface of the transfected cells and short microtubules starting from the cell center. After differentiation in the presence of DBcAMP + NGF, the same bundle organization was observed in the transfected cells. In addition, tau and MAP2 antibodies stained a short section of the formed neurites. These data demonstrate that the expression of tau protein is not sufficient to induce neurite extension and that other proteins induced by morphogens are more important to initiate morphological differentiation of this cell line.
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PMID:Tau and microtubule-associated protein 2c transfection and neurite outgrowth in ND 7/23 cells. 786 Nov 33

The apolipoprotein E type 4 allele is a susceptibility gene for late-onset Alzheimer's disease. Apolipoprotein E is found in neurons, some of which contain paired helical filaments made of the microtubule-associated protein tau. Previous studies have demonstrated that the apoE3 isoform, but not the apoE4 isoform, binds tau with high avidity. Because the microtubule-associated protein MAP2c also effects microtubule assembly and stability, we examined interactions between apoE isoforms and MAP2c. Similar to the tau-binding results, apoE3, but not apoE4, bound MAP2c. Binding was detectable down to 10(-9) M MAP2c and 10(-8) M apoE3. Isoform-specific interactions of apoE with the microtubule-associated proteins MAP2c and tau might affect intracellular maintenance of microtubules and could contribute to a time-dependent pathogenesis of Alzheimer's disease.
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PMID:Isoform-specific interactions of apolipoprotein E with the microtubule-associated protein MAP2c: implications for Alzheimer's disease. 789 87

We previously showed that neurofilaments interact with microtubules (MTs) via their high molecular weight subunits (NF-H) after alkaline phosphatase treatment. Here we studied the effects of phosphorylation of NF-H on this interaction. tau protein kinase II, Ser/Thr protein kinase, phosphorylated NF-H in the tail domain, decreased its electrophoretic mobility to a native level, and also restored its property to be less interactive with MTs. Phosphorylation by cAMP-dependent protein kinase caused no shift of electrophoretic mobility or dissociation from MTs. We conclude that the tail domain of NF-H directly interacts with the MT surface, and the interaction is regulated via phosphorylation of the tail domain of NF-H by Ser/Thr protein kinase like tau protein kinase II. To characterize the binding domain of NF-H on MTs, subtilisin digestion of MTs and competition analysis with the MT binding fragment of tau protein were performed. The dissociation constant of NF-H to subtilisin MTs was higher than that to intact MTs. The maximum binding of NF-H was reduced when tau fragments existed. These results revealed that the COOH-terminal region of tubulin is involved in the binding to NF-H, and the NF-H and microtubule-associated protein binding domains are closely apposed on the surface of MTs.
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PMID:Interaction of the tail domain of high molecular weight subunits of neurofilaments with the COOH-terminal region of tubulin and its regulation by tau protein kinase II. 822 79

Brain proline-directed protein kinase (BPDK), which contains a catalytic subunit homologous to and displaying site-specific phosphorylation similar to p34cdc2 kinase (Lew, J., Winkfein, R. J., Paudel, H. K., and Wang, J. H. (1992) J. Biol. Chem. 267, 25922-25926), has been examined for possible involvement in tau phosphorylation. Immunoblot analyses using peptide antibodies specific for BPDK have revealed the presence of the kinase in bovine brain microtubules purified extensively by repeated polymerization and depolymerization cycles. When the microtubule proteins are separated into the tubulin and microtubule-associated protein fractions, BPDK is found exclusively in the latter fraction. BPDK phosphorylates both tau and MAP2, the former protein being phosphorylated to a stoichiometry of 3.8 mol of phosphate/mol of tau. Analysis of the phosphopeptides isolated from the tryptic digest of the phosphorylated bovine tau has revealed seven phosphorylation sites. Based on the sequence alignment between bovine and human tau proteins, these sites correspond to Ser-195, Ser-202, Thr-205, Thr-231, Ser-235, Ser-396, and Ser-404 of human tau. Mass spectrometric analysis of the tau protein isolated from Alzheimer's paired helical filaments (PHFs) has determined three abnormal phosphorylation sites and two phosphopeptides containing a total of five abnormal phosphates (Hasegawa, M., Morishima-Kawashima, M., Takio, K., Suzuki, M., Titani, K., and Ihara, Y. (1992) J. Biol. Chem. 267, 17047-17054). Two of the sites in tau phosphorylated by BPDK, Thr-231 and Ser-235, are among the abnormal phosphorylation sites, and the other sites phosphorylated by BPDK are within phosphopeptides from PHF-tau. These results suggest that BPDK may be one of the kinases responsible for the abnormal phosphorylation-associated PHF-tau.
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PMID:Brain proline-directed protein kinase phosphorylates tau on sites that are abnormally phosphorylated in tau associated with Alzheimer's paired helical filaments. 822 79

Tau protein is a microtubule-associated protein that is almost exclusively expressed in the brain and is enriched in the axon. Determination of tau's sequence has revealed three to four tandem repeats that have been shown to constitute the microtubule binding site. In order to study the functional organization of tau, we prepared a series of truncated tau fragments using an Escherichia coli expression system. We assayed each fragment's activity in promoting growth of microtubules and in nucleating free microtubules. We found that tau's ability to nucleate microtubules requires the presence of additional sequence amino-terminal to that required for growth. We demonstrate that tau's carboxyl and amino termini differentially affect microtubule growth and nucleation. Finally, we show that in vitro microtubule bundle formation occurs when tubulin is assembled in the presence of an amino- and carboxyl-terminally truncated tau protein, whereas almost no bundling is observed in the presence of full-length tau or tau fragments that contain the amino terminus in addition to the repeat domain. We conclude that although the presence of the repeat domain promotes the growth of microtubules, the structural requirements for nucleation activity are more stringent. The differentiation between the growth promoting and nucleation activities on the structural level makes it possible for the two activities to be differentially regulated in vivo.
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PMID:Functional organization of microtubule-associated protein tau. Identification of regions which affect microtubule growth, nucleation, and bundle formation in vitro. 842 17

Tau protein is a phosphorylated neuronal microtubule-associated protein. Tau protein is also present in the major pathological lesions of Alzheimer's disease in an insoluble hyperphosphorylated state as paired helical filaments (PHFs). We have investigated the phosphorylation state of control taus and a fragment of PHF-tau. Tau samples were digested with protease, separated by reversed-phase high-performance liquid chromatography, and analyzed by mass spectrometry and Edman microsequencing. The serine homologous with S404 of human tau 441 was phosphorylated on bovine and porcine tau and up to two phosphates were present on a peptide of amino acids 182-240 of bovine tau (193-251 of human tau 441). The serine within the KSPV motif was not phosphorylated on bovine or porcine tau. PHF-tau fragments, isolated from pronase-treated PHFs encompassed a 93-amino acid region within the microtubule binding domain. Enzymatic digestion and mass spectrometric analysis showed no phosphate was present and a second carboxyl terminus was identified at E380. Antibodies T3P and SMI34, which recognize PHF-tau and peptides phosphorylated at the sequence KSPV, both reacted with bovine and porcine tau even though the KSPV sequence was not phosphorylated. These data indicate that the 93-amino acid sequence of F5.5 tau from PHFs is not phosphorylated, and the serine equivalent to S404 of human tau is phosphorylated in bovine and porcine tau. Antibodies T3P and SMI34 react with phosphorylated epitopes that are not unique to PHF-tau and that are not necessarily at the KSPV site.
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PMID:Locations and immunoreactivities of phosphorylation sites on bovine and porcine tau proteins and a PHF-tau fragment. 848 51


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