Tau protein: An update on structure and function

Lee, Gloria

doi:10.1002/cm.970150402

Cited by 83 publications

(37 citation statements)

References 28 publications

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“…Tau is a phosphoprotein and phosphorylation is known to regulate its microtubule polymerization and stabilization abilities [3][4][5][6]. In particular, currently phosphorylation of tau has attracted much attention, because of the fact that the highly phosphorylated form of tau is a main component of the paired helical filaments (PHFs) found in Alzheimer's disease brains [7][8][9].…”

Section: Introduction 2 Materials and Methodsmentioning

confidence: 99%

In situ dephosphorylation of tau by protein phosphatase 2A and 2B in fetal rat primary cultured neurons

et al. 1995

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Key words: Protein phosphatase; Tau; Microtubule-associated protein; Primary cultured neuron; cdk5However, the broad substrate specificity of protein phosphatases [20,21] makes it uncertain that these protein phosphatases indeed act on tau in vivo. To resolve this question, we used rat primary cultured neurons and examined which protein phosphatase dephosphorylates which phosphorylation sites of tau. We chose to use cultured neurons because they are amenable to treatments with protein phosphatase inhibitors. Another advantage of using fetal brain neurons was the expression of a single tau species, which differ from adult rat brain in which complicated expression patterns of alternatively spliced isoforms might hinder the observation of phosphorylation-dependent electrophoretic mobility shift [22][23][24]. Finally, the use of antibodies that can recognize a single site-specific phosphorylation is also a considerable technical improvement over other systems. We report here our findings that PP2A and PP2B are capable of dephosphorylating tau in a site-specific and Ca2+-dependent manner.

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Section: Introduction 2 Materials and Methodsmentioning

confidence: 99%

In situ dephosphorylation of tau by protein phosphatase 2A and 2B in fetal rat primary cultured neurons

et al. 1995

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“…DISCUSSION We have purified proteins that enhance the activity of PLC-␥1 toward a micellar substrate containing PI and deoxycholate and identified them as tau isoforms. Tau comprises a family of microtubule-associated proteins that are generated from alternatively spliced transcripts derived from a single gene with 13 exons (reviewed by Lee (1990)). Tau expression is largely restricted to brain and is developmentally regulated.…”

Section: Effect Of Pc On Tau-and Aa-dependent Plc-␥1 Activity-mentioning

confidence: 99%

“…Tau proteins are predominantly expressed in neuronal tissue (Lee 1990;Mandelkow and Mandelkow, 1993). However, the above examples of the potential linkage between AA and PLC activation include both neuronal and non-neuronal cells.…”

Section: Effect Of Pc On Tau-and Aa-dependent Plc-␥1 Activity-mentioning

confidence: 99%

Activation of Phospholipase C-γ by the Concerted Action of Tau Proteins and Arachidonic Acid

Hwang

Jhon

Bae

et al. 1996

Journal of Biological Chemistry

165

102

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Phospholipase C-␥ (PLC-␥) isozymes are thought to be activated by receptor-induced tyrosine phosphorylation. Proteins that activate PLC-␥1 have now been purified from bovine brain and identified as members of the tau family of microtubule-associated proteins. Activation of PLC-␥ by tau was enhanced in the presence of unsaturated fatty acids such as arachidonic acid, saturated fatty acids being ineffective. Maximal (15-20-fold) activation was apparent in the presence of 0.15 M tau and 25 M arachidonic acid (AA). The effect of tau and AA was specific to PLC-␥ isozymes in the presence of submicromolar concentrations of Ca 2؉ and was markedly inhibited by phosphatidylcholine. These results suggest that in cells that express tau, receptors coupled to cytosolic phospholipase A 2 may activate PLC-␥ isozymes indirectly in the absence of tyrosine phosphorylation through the hydrolysis of phosphatidylcholine to generate AA.The hydrolysis of a minor membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP 2 ), 1 by a specific phospholipase C (PLC) is one of the earliest key events in the regulation of cellular function by more than 100 different extracellular signaling molecules (reviewed by Noh et al. (1995)). This reaction generates two intracellular messengers: inositol 1,4,5-trisphosphate (IP 3 ), which induces the release of Ca 2ϩ from internal stores, and diacylglycerol, which activates protein kinase C.Ten mammalian isoforms of PLC have been identified to date, and these can be divided into ␤ type (PLC-␤1, -␤2, -␤3, and -␤4), ␥ type (PLC-␥1 and -␥2), and ␦ type (PLC-␦1, -␦2, -␦3, and -␦4) enzymes on the basis of amino acid sequence (Noh et al., 1995). The distinct structural features of the different PLC types have been related to specific mechanisms of receptormediated enzyme activation. Thus, PLC-␥ isozymes are activated by tyrosine phosphorylation, and PLC-␤ isozymes are activated by heterotrimeric G proteins (Noh et al., 1995); the mechanism of PLC-␦ isozyme activation is not known.PLC hydrolyzes phosphatidylinositol (PI) and phosphatidylinositol 4-phosphate as well as the physiological substrate, PIP 2 , in vitro, with PI-hydrolyzing activity often measured during PLC purification. While purifying PLC-␥1, the most abundant PLC isoform in brain cytosol, we observed that the PI-hydrolyzing activity of crude brain cytosol decreased more than expected on dilution. Furthermore, addition of crude cytosol to purified PLC-␥1 markedly enhanced PI-hydrolyzing activity. These observations suggested that brain cytosol contains a component that can enhance the activity of PLC-␥1 toward PI.We now describe the purification of this activator and its identification as the microtubule-associated protein tau. We also show that tau enhances the activity of PLC-␥1 toward PIP 2 to a markedly lesser extent than that apparent with PI and that the effect of tau on PLC-␥ activity toward PIP 2 is greatly increased in the presence of arachidonic acid (AA). Of the three types of PLC, the ␥ type isozymes are most sensitive to activ...

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“…The tau protein family consists of six isoforms generated by alternative splicing from one gene, whicll are highly conserved between mammalian species, and are subject to phosphorylation [4,5]. Modified tau protein is the main part of the characteristic paired helical filaments that appear during neuronal degeneration in Alzheimer disease [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…Mierotubules are formed by assembly of gB-tubulin, and a number of microtubale-associated proteins (MAPs) and microtubalebased motors, which bind to their surface and provide the regulation and functionalities to these organdies. High molecular weight MAPs include MAPIA, MAPIB, MAP1C (cytoplasmic dynein) MAP2A, MAP2B and MAPU/MAP4; lower molecular weight MAPs include low molecular weight forms of" MAP2, and the tau factor [2,3].The tau protein family consists of six isoforms generated by alternative splicing from one gene, whicll are highly conserved between mammalian species, and are subject to phosphorylation [4,5]. Modified tau protein is the main part of the characteristic paired helical filaments that appear during neuronal degeneration in Alzheimer disease [6,7].…”

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confidence: 99%

Chemically synthesized 182–235 segment of tau protein and analogue peptides are efficient in vitro microtubule assembly inducers of low apparent sequence specificity

Novella

Andreu

1992

FEBS Letters

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A 54-amino acid peptide reproducing the first and second repeats and intervening spacer sequence of the tubulin binding motif (residues 182-235) of murine tau protein, and ~everal congeners representing different degrees of ~equence scrambling have been prepared by solid phase methods and fully characterized chemically. These double-repeat peptides have been sl~own to induce microtubule formation at concentrations abaut one order of magnitude lower than single.repeat controls, under conditions close to the critical concemration needed for tabalin sdf-asscmbly. On the other hand. partial loss of mierotubule-inducing capacity was observed for peptide5 with primary structures increasingly disorganized with respect to the canonical pcptide. These r~ults call into question the assumption that a high degree of primary structure specificity is involved in the tau-tubulin interaction leading to in vitro microtubale formation.Tubulin assembly; Tau sequence specificity; Solid phase peptide synthesis 1, INTRODUCTIONMicrotubules are eukaryotic organelles involved in a wide variety of biological functions such as mitosis, motility, intracellular transport and establishment and nmintenance of cell shape [1]. Mierotubules are formed by assembly of gB-tubulin, and a number of microtubale-associated proteins (MAPs) and microtubalebased motors, which bind to their surface and provide the regulation and functionalities to these organdies. High molecular weight MAPs include MAPIA, MAPIB, MAP1C (cytoplasmic dynein) MAP2A, MAP2B and MAPU/MAP4; lower molecular weight MAPs include low molecular weight forms of" MAP2, and the tau factor [2,3].The tau protein family consists of six isoforms generated by alternative splicing from one gene, whicll are highly conserved between mammalian species, and are subject to phosphorylation [4,5]. Modified tau protein is the main part of the characteristic paired helical filaments that appear during neuronal degeneration in Alzheimer disease [6,7]. An important feature in the sequence of tau protein is the presence of three or four 18-residue imperfect repeats, separated by 13-or 14-residue linkers, which are believed to constitute a tu- An important problem in microtubule assembly, regulation and function consists in understanding how these MAP microtubul¢ binding modules, which contain abundant basic residues, bind to the acidic tubulin molecules within the ordered surface lattice of the microtubule wall, in a muitivalent inter:tction. This interaction should have a large electrostatic component, although hydrophobic contacts appear to be involved [12].The role of the tau/MAP2 repeats has been studied by two different approaches, employing either genetically engineered constructs or MAP fragments prepared by chemical synthesis. Transfection of cells with deletion constructs of MAP2 and tau indicated the requirement of at least one repeat to bind to microtubules [13]. Employing tau eDNA clones from human fetal brain and an E. coli expression system it was shown that fragments containing three, two or...

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Tau protein: An update on structure and function

Cited by 83 publications

References 28 publications

In situ dephosphorylation of tau by protein phosphatase 2A and 2B in fetal rat primary cultured neurons

In situ dephosphorylation of tau by protein phosphatase 2A and 2B in fetal rat primary cultured neurons

Activation of Phospholipase C-γ by the Concerted Action of Tau Proteins and Arachidonic Acid

Chemically synthesized 182–235 segment of tau protein and analogue peptides are efficient in vitro microtubule assembly inducers of low apparent sequence specificity

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